Next Article in Journal
COVID-19: Where We Are and Where We Are Going
Previous Article in Journal
Reproductive Health Practices in Spanish Women Who Underwent Voluntary Termination of Pregnancy
Previous Article in Special Issue
Yata Virus (Family Rhabdoviridae, Genus Ephemerovirus) Isolation from Mosquitoes from Uganda, the First Reported Isolation since 1969
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:

A Brief History of Bunyaviral Family Hantaviridae

Jens H. Kuhn
* and
Connie S. Schmaljohn
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD 21702, USA
Authors to whom correspondence should be addressed.
Diseases 2023, 11(1), 38;
Submission received: 20 December 2022 / Revised: 16 February 2023 / Accepted: 20 February 2023 / Published: 28 February 2023


The discovery of Hantaan virus as an etiologic agent of hemorrhagic fever with renal syndrome in South Korea in 1978 led to identification of related pathogenic and nonpathogenic rodent-borne viruses in Asia and Europe. Their global distribution was recognized in 1993 after connecting newly discovered relatives of these viruses to hantavirus pulmonary syndrome in the Americas. The 1971 description of the shrew-infecting Hantaan-virus-like Thottapalayam virus was long considered an anomaly. Today, this virus and many others that infect eulipotyphlans, bats, fish, rodents, and reptiles are classified among several genera in the continuously expanding family Hantaviridae.

1. Introduction

What is a “hantavirus”? In 1983, the answer seemed relatively straightforward: Less than a dozen serologically, morphologically, and genetically related non-arthropod-borne viruses, each associated with distinct persistently infected rodent hosts, constituted a tight virus clade related to, but separate from, similar viruses carried by or transmitted by arthropod vectors. These rodent-borne viruses were known to be transmitted among rodents and occasionally to humans in aerosols of rodent urine, feces, or saliva or through biting/wounding. Several hantaviruses were found to cause a mild, moderate, or severe disease in humans called “hemorrhagic fever with renal syndrome (HFRS)”, with humans being dead-end hosts [1,2,3]. Accordingly, a new genus was proposed for this group of viruses and named Hantavirus after the founding member, Hantaan virus (HTNV) [3,4]. This genus was accepted by the International Committee on Taxonomy of Viruses (ICTV) in 1987 and included in the family Bunyaviridae [5,6].
In 1993, a novel hantavirus was associated with a highly lethal acute respiratory distress syndrome, hantavirus pulmonary syndrome, in the southwestern U.S., spurring intense additional hantavirus research and rapid progress in the identification of many more hantaviruses around the world [7,8]. Each novel discovery in relation to these viruses eroded previous definitions of the term “hantavirus”. Here, we briefly recount the story of these viruses, from the first isolation of HTNV to the promotion of the genus Hantavirus in the family Bunyaviridae to the family Hantaviridae in the order Bunyavirales [9]. This is not intended to be a comprehensive review of Hantaviridae but rather a primer on the history and possible future of this family of viruses.

2. Diseases in Search of Viruses

“Korean hemorrhagic fever”, also called “epidemic hemorrhagic fever”, was a disease of unknown etiology that occurred among several thousand United Nations troops during the Korean War (1950–1953). At the height of the conflict, in 1951, hundreds of U.S. military personnel were hospitalized with fever and oral, nasal, and internal hemorrhages; these cases sometimes led to fatalities related to renal failure and shock [10,11]. There was a long history of cases with similar clinical presentation: The disease was likely first outlined in the Yellow Emperor’s Internal Canon (黃帝內經) in Imperial China during the Warring States Period (475–221 BCE) [12] and then noted during World War I after affecting British soldiers in Flanders, Belgium [13,14,15]. The first definite clinical/scientific descriptions came from Asia and Europe in and after 1932 [16]. However, there was no known relationship among them, nor was any causative pathogen identified for any of these diseases.
An important breakthrough was made in 1976, when antigen in the lungs of striped field mice (Apodemus agrarius (Pallas, 1771)), trapped in several locations of South Korea, was shown to react with antibodies in sera from Korean hemorrhagic fever patients. Although an agent could not be isolated in cell culture at that time, seven successive passages of antigen-positive lung tissue in adult striped field mice demonstrated that an infectious agent was present. Antisera from patients with various hemorrhagic fevers of known etiologies did not react with this agent, implying that it was likely novel [17,18,19].

2.1. The Beginning of the Hantavirology

Propagation of the novel virus in cell culture was finally reported in 1981 [20]. The virus, termed “KHF strain 76-118”, originated from naturally infected rodents trapped near Songnaeri (송내리) and passed through naïve striped field mice four times prior to the isolation attempt. The isolated virus was renamed “Hantaan virus, strain 76-118” after the Hantan River, (한탄강), a tributary of the Imjin River (임진강), which crosses the Demilitarized Zone that separates North Korea and South Korea.
The initial clue to the taxonomic position of HTNV came from electron microscopic examination of HTNV particles, which revealed a morphology akin to that of particles of other viruses then classified in the family Bunyaviridae [21,22]. This presumptive evidence was soon corroborated by the biochemical characterization of purified HTNV particles and viral components. Consistent with other viruses in that family, HTNV particles were enveloped and contained three separate nucleocapsid structures encapsulating distinct genomic RNAs [2]. These findings were surprising, as most scientists studying Korean/epidemic hemorrhagic fever expected the etiologic agent to be related to viruses causing Argentinian or Bolivian hemorrhagic fevers (i.e., Junín virus and Machupo virus, respectively, of the family Arenaviridae). This expectation was rooted in findings that HTNV, similar to Junín and Machupo viruses, is carried and transmitted by rodents, whereas all then-known members of the family Bunyaviridae were vectored by insects or ticks.
Around the time of the initial HTNV characterization, it became clear that this virus was the founding member of a larger group. By 1980, studies had confirmed that viruses closely related to or identical to HTNV caused long-known diseases with similar clinical presentations as ‘Korean/epidemic hemorrhagic fever’ in China, Japan, Scandinavia, and the USSR [17,23,24,25,26,27]. In 1982, the World Health Organization (WHO) sponsored a conference to discuss these diseases, which were known by a variety of names (e.g., hemorrhagic nephroso-nephritis and nephropathia epidemica) [28]. A recommendation was made that all of these diseases be collectively re-termed “haemorrhagic fever with renal syndrome (HFRS)” [29], and this term is still the official disease name in today’s 11th revision of WHO’s International Classification of Diseases (ICD-11), under the “hantavirus disease” subcode 1D62.0 [30].

2.2. A New Genus

Molecular and antigenic characterization of HTNV revealed additional properties consistent with viruses classified in the Bunyaviridae family, such as ribonuclease-sensitive nucleocapsids, a virion-associated polymerase, and two envelope glycoproteins [2,4,31,32]. However, HTNV did not serologically cross-react with viruses from the four then-recognized genera in the Bunyaviridae family (Bunyavirus, Nairovirus, Phlebovirus, and Uukuvirus), indicating that the epitopes and HTNV are distinct. The viruses assigned to these genera have conserved 3′ and 5′ complementary nucleotides on each of their three genome segments that form panhandle-like secondary structures important for viral transcription and replication. These nucleotides were identical in the genomes of all viruses of a given genus but differed among genera. Indeed, sequencing of the HTNV genome segments revealed a conserved string of 3′ nucleotides among all three segments, but these were distinct from those in the genomes of viruses assigned to the established genera. This finding led to the suggestion in 1983–1984 that HTNV and related viruses should form a new genus [2,3].
By 1985, several other HTNV-like viruses (e.g., those that today are known as Prospect Hill virus [PHV], Puumala virus [PUUV], and Seoul virus [SEOV]) had been isolated from various rodents and clinical samples from HFRS patients. A collaborative effort to characterize these viruses further supported the need for a unique genus [33]. A proposal was submitted to the ICTV, which accepted the addition of the new genus Hantavirus to the family Bunyaviridae in 1987 [6]. The Fifth ICTV Report of 1991 described the genus as follows:
“There is one recognized group within the genus Hantavirus (at least six viruses), plus a large number of isolates not yet assigned to an antigenic complex; serologically unrelated to members of other genera; probably no arthropod vector involved in transmission”
From then on, the genus Hantavirus changed through the addition and sometimes removal of rodent-borne viruses. In line with nomenclature conventions applied to other genera, the members of the genus Hantavirus were henceforth referred to as “hantaviruses”.

2.3. A New Disease

In 1993, hantavirology took an unexpected turn when the etiology of a highly lethal acute respiratory distress syndrome in humans living in the southwestern U.S. was found to be a hantavirus [7,8,34] distinct from all then-known hantaviruses [8,35,36]. Since the disease occurred in the Four Corners region of the U.S. (where Arizona, Colorado, New Mexico, and Utah intersect), the virus was originally named “Four Corners virus” [36]. This name and several others brought forward by researchers did not last due to various concerns about political implications. Finally, the U.S. Centers for Disease Control and Prevention (CDC) settled on the name “Sin Nombre virus (SNV)”. The new disease (later traced back to at least 1959 [37]) was termed “hantavirus pulmonary syndrome (HPS)” [7], and this name is still in use today (ICD-11 hantavirus disease subcode 1D62.0 [30]). SNV was first identified as being carried by North American deermice (former Peromyscus maniculatus (J. A. Wagner, 1845, sensu lato)) [38], it is known to comprise two separate clades: eastern deermice (Peromyscus maniculatus (J. A. Wagner, 1845, sensu stricto)) and western deermice (Peromyscus sonoriensis (J. A. Wagner, 1845)) [39]. However, recent evidence indicates that deermice of many more species are susceptible to SNV infection [40].
During subsequent years, many additional HPS-causing and presumed apathogenic relatives were identified in rodents of several other species throughout the Americas. Andes virus (ANDV) was identified in 1996 in South America and is carried by long-tailed colilargos (Oligoryzomys longicaudatus (Bennett, 1832)). Several closely related, if not identical, viruses stand out as being the only hantaviruses known to be associated with person-to-person transmission [41,42,43,44,45].

3. Viruses in Search of Diseases

The original concept that hantaviruses were strictly associated with rodents was challenged in the early 1990s by the realization that Thottapalayam virus (TPMV), isolated in 1965 from a soricid Asian house shrew (Suncus murinus (Linnaeus, 1766)) in India [46], was clearly related to the then-known hantaviruses [5,47,48,49]. Long ignored as a possible artifact, the ecological association of TPMV with shrews was confirmed in 2007 [50], thereby adding eulipotyphlans to the hantavirus host spectrum. Evidence of hantaviruses other than TPMV possibly infecting soricid shrews and talpid moles was accumulated between 1983 and 1990 [51,52,53,54,55,56,57,58,59,60]. However, in 2007, the first unequivocal identifications of non-TPMV soricid hantaviruses were reported via the description of Seewis virus (SWSV) in common shrews (Sorex (Sorex) araneus Linnaeus, 1758), captured in Switzerland [61]; “Camp Ripley virus” in northern short-tailed shrews (Blarina brevicauda (Say, 1823)), captured in the U.S. [62]; Cao Bằng virus (CBNV) in Chinese mole shrews (Anourosorex squamipes Milne-Edwards, 1872), captured in Vietnam [63]; and “Tanganya virus” in the Therese’s shrews (Crocidura theresae Heim de Balsac, 1968), captured in Guinea [64]. Since then, at least another 13 soricid hantaviruses have been discovered in Africa, Asia, Europe, and North America [65]. In 2008, the first talpid hantavirus, Asama virus (ASAV), was described after its discovery in Japanese shrew moles (Urotrichus talpoides Temminck, 1841) [66]. At least seven additional talpid mole viruses have since been discovered in Asia, Europe, and North America [65,67,68].
Hantaviruses have been suspected of infecting bats (order Chiroptera) in addition to mammals of the orders Rodentia and Eulipotyphla since 1994 [69,70]. The first confirmation of this hypothesis was published in 2012, when “Magboi virus” was discovered in nycterid hairy slit-faced bats (Nycteris hispida (Schreber, 1775)), sampled in Sierra Leone [71]. At least 11 other bat hantaviruses were discovered thereafter in Africa, Asia, and Europe, spanning hosts of both chiropteran suborders Yinpterochiroptera (Hipposideridae, Pteropodidae, and Rhinolophidae) and Yangchiroptera (Emballonuridae, Molossidae, Nycteridae, and Vespertilionidae) [65,72,73].
Hantavirology took another unexpected turn with the metagenomic discovery of three distinct hantaviruses in saltwater actinopterygiid fish of three orders, captured in the South China Sea; one new hantavirus in freshwater actinopterygiid fish, sampled in Europe; one new hantavirus in myxinid fish, captured in the South China Sea; and one new hantavirus in a gekkotan reptile [74,75]. The most recent discovery of additional hantavirus nucleic acids in Australian actinopterygiid freshwater fish and scincomorphan reptiles [76,77,78] suggests that there are many more fish and reptile hantaviruses.
Together, these findings finally abolished the “rodent virus” and “mammal virus” monikers for hantaviruses. At least for now, one dogma still stands: Only rodent-borne hantaviruses have been associated with human disease. Whether the other hantaviruses also have the potential for human spillover or whether they cause diseases in animals other than humans remains to be determined through careful study of these mostly completely uncharacterized agents.

4. A New Taxonomy

The hantavirus clade was not the only virus group that greatly expanded over recent decades. Hundreds of novel viruses were easily assignable to the Bunyaviridae family, and dozens of them could be included in the four established Hantavirus sister genera (Bunyavirus, Nairovirus, Phlebovirus [by then including the members of then-abolished genus Uukuvirus], and Tospovirus). With this expansion, the advent of improved genome sequencing methodologies, and new tools to probe phylogeny, came the realization that the true diversity and the evolutionary relationship of all these viruses could not be adequately depicted in a three-taxon (family, genus, species) hierarchy; distinct subclades of viruses became discernible in each of the genera, and entire, complex, new virus clades, apparently sister to the established genera, needed to be added. In 2017, family Bunyaviridae was therefore promoted to the Bunyavirales order; in parallel, the five genera were promoted to families (BunyavirusPeribunyaviridae; HantavirusHantaviridae; NairovirusNairoviridae; PhlebovirusPhenuiviridae; and TospovirusTospoviridae) to enable high-resolution classification of their members at the genus rank [9].
To remove possible ambiguities associated with the vernacular term “hantavirus”, a new genus, Orthohantavirus, was created within Hantaviridae in 2018 [9]. Thereafter, genus members were to be referred to as “orthohantaviruses” and family members as “hantaviruses”, or, preferably, “hantavirids”, using the vernacular family-specific suffix “-virid(s)” to clarify family references in communication [79]. Importantly, throughout the dramatic expansion of known bunyavirals, hantavirids remained a highly distinct and therefore easily identifiable clade, and DivErsity pArtitioning by hieRarchical Clustering (DEmARC) analysis confirmed most well-characterized hantavirids to be clearly distinct entities [80]. Ironically, this analysis also revealed that eulipotyphlan TPMV formed a sister group with most other eulipotyphlan and all rodent orthohantaviruses. Bat viruses fell into separate sister clades. Thus, in 2019, the family was expanded by three genera: Loanvirus (bat viruses), Mobatvirus (bat and eulipotyphlan viruses), and Thottimvirus (TPMV and other eulipotyphlan relatives) [81]. Furthermore, in 2019, genera Actinovirus (Actinopterygiid viruses), Agnathovirus (Myxinid viruses), and Reptillovirus (Reptilian viruses) were added to the family, which was further subdivided into four subfamilies: Acanthavirinae (Actinovirus), Agantavirinae (Agnathovirus), Mammantavirinae (Loanvirus, Mobatvirus, Orthohantavirus, Thottimvirus), and Repantavirinae (Reptillovirus) [82]. The most up-to-date composition of Hantaviridae [83] is outlined in Table 1.
Table 1. 2022 [83] and projected 2023 [84] taxonomies of the bunyaviral family Hantaviridae.
Table 1. 2022 [83] and projected 2023 [84] taxonomies of the bunyaviral family Hantaviridae.
GenusSpecies Name (2022)Projected Species Name (2023)Virus Name (Abbreviation)Human Disease
Subfamily Acanthavirinae (hosted by fish)/
ActinovirusBatfish actinovirusActinovirus halieutaeaeWēnlǐng minipizza batfish virus (WEMBV)/
Goosefish actinovirusActinovirus lophiiWēnlǐng yellow goosefish virus (WEYGV)/
Perch actinovirusActinovirus bernenseBern perch virus (BRPV)/
Spikefish actinovirusActinovirus triacanthodisWēnlǐng red spikefish virus (WERSV)/
Subfamily Agantavirinae (hosted by fish)
AgnathovirusHagfish agnathovirusAgnathovirus eptatretiWēnlǐng hagfish virus (WEHV)/
Subfamily Mammantavirinae (hosted by bats, moles, shrews, and rodents)
LoanvirusBrno loanvirusLoanvirus brunaenseBrno virus (BRNV)/
Longquan loanvirusLoanvirus longquanenseLóngquán virus (LQUV)/
MobatvirusLaibin mobatvirusMobatvirus laibinenseLáibīn virus (LAIV)/
Lena mobatvirusMobatvirus lenaenseLena virus (LENV)/
Nova mobatvirusMobatvirus novaenseNova virus (NVAV)/
Quezon mobatvirusMobatvirus quezonenseQuezon virus (QZNV)/
Xuan Son mobatvirusMobatvirus xuansonenseXuân Sơn virus (XSV)/
OrthohantavirusAndes orthohantavirusOrthohantavirus andesenseAndes virus (ANDV)HPS
Castelo dos Sonhos virus (CASV)HPS
Lechiguanas virus (LECV = LECHV)HPS
Orán virus (ORNV)HPS
Asama orthohantavirusOrthohantavirus asamaenseAsama virus (ASAV)/
Asikkala orthohantavirusOrthohantavirus asikkalaenseAsikkala virus (ASIV)/
Bayou orthohantavirusOrthohantavirus bayouibayou virus (BAYV)HPS
Catacamas virus (CATV)HPS
Black Creek Canal orthohantavirusOrthohantavirus nigrorivenseBlack Creek Canal virus (BCCV)HPS
Bowe orthohantavirusOrthohantavirus boweenseBowé virus (BOWV)/
Bruges orthohantavirusOrthohantavirus brugesenseBruges virus (BRGV)/
Cano Delgadito orthohantavirusOrthohantavirus delgaditoenseCaño Delgadito virus (CADV)/
Cao Bang orthohantavirusOrthohantavirus caobangenseCao Bằng virus (CBNV)/
Liánghé virus (LHEV)/
Choclo orthohantavirusOrthohantavirus chocloenseChoclo virus (CHOV)HPS
Dabieshan orthohantavirusOrthohantavirus dabieshanenseDàbiéshān virus (DBSV)/
Dobrava-Belgrade orthohantavirusOrthohantavirus dobravaenseDobrava virus (DOBV)HFRS
Kurkino virus (KURV)HFRS
Saaremaa virus (SAAV)HFRS
Sochi virus (SOCV)HFRS
El Moro Canyon orthohantavirusOrthohantavirus moroenseCarrizal virus (CARV)/
El Moro Canyon virus (ELMCV)HPS
Huitzilac virus (HUIV)/
Fugong orthohantavirusOrthohantavirus fugongenseFúgòng virus (FUGV)/
Fusong orthohantavirusOrthohantavirus fusongenseFǔsōng virus (FUSV)/
Hantaan orthohantavirusOrthohantavirus hantanenseAmur virus (AMRV)HFRS
Hantaan virus (HTNV)HFRS
Soochong virus (SOOV)/
Jeju orthohantavirusOrthohantavirus jejuenseJeju virus (JJUV)/
Kenkeme orthohantavirusOrthohantavirus kenkemeenseKenkeme virus (KKMV)/
Khabarovsk orthohantavirusOrthohantavirus khabarovskenseKhabarovsk virus (KHAV)/
Topografov virus (TOPV)/
Laguna Negra orthohantavirusOrthohantavirus negraenseLaguna Negra virus (LANV)HPS
Maripa virus (MARV)HPS
Rio Mamoré virus (RIOMV)HPS
Luxi orthohantavirusOrthohantavirus luxienseLúxī virus (LUXV)/
Maporal orthohantavirusOrthohantavirus maporalenseMaporal virus (MAPV)/
Montano orthohantavirusOrthohantavirus montanoenseMontaño virus (MTNV)/
Necocli orthohantavirusOrthohantavirus necoclienseNecoclí virus (NECV)/
Oxbow orthohantavirusOrthohantavirus oxbowenseOxbow virus (OXBV)/
Prospect Hill orthohantavirusOrthohantavirus prospectenseProspect Hill virus (PHV)/
Puumala orthohantavirusOrthohantavirus puumalaenseHokkaido virus (HOKV)/
Muju virus (MUJV)HFRS
Puumala virus (PUUV)HFRS
Robina orthohantavirusOrthohantavirus robinaenseRobina virus (ROBV) */
Rockport orthohantavirusOrthohantavirus rockportenseRockport virus (RKPV)/
Sangassou orthohantavirusOrthohantavirus sangassouenseSangassou virus (SANGV)/
Seewis orthohantavirusOrthohantavirus seewisenseSeewis virus (SWSV)/
Seoul orthohantavirusOrthohantavirus seoulensegōu virus (GOUV)HFRS
Seoul virus (SEOV)HFRS
Sin Nombre orthohantavirusOrthohantavirus sinnombreenseNew York virus (NYV)HPS
Sin Nombre virus (SNV)HPS
Tatenale orthohantavirusOrthohantavirus tatenalenseTatenale virus (TATV)/
Thailand orthohantavirusOrthohantavirus thailandenseAnjozorobe virus (ANJZV)/
Serang virus (SERV)/
Thailand virus (THAIV)/
Tigray orthohantavirusOrthohantavirus tigrayenseTigray virus (TIGV)/
Tula orthohantavirusOrthohantavirus tulaenseAdler virus (ADLV)/
Tula virus (TULV)HFRS
Yakeshi orthohantavirusOrthohantavirus yakeshienseYákèshí virus (YKSV)/
ThottimvirusImjin thottimvirusThottimvirus imjinenseImjin virus (MJNV)/
Thottapalayam thottimvirusThottimvirus thottapalayamenseThottapalayam virus (TPMV)/
Subfamily Repantavirinae (hosted by reptiles)
ReptillovirusGecko reptillovirusReptillovirus hemidactyliHǎinán oriental leaf-toed gecko virus (HOLGV)/
HFRS, hemorrhagic fever with renal syndrome (ICD-11 hantavirus disease subcode 1D62.0); HPS, hantavirus pulmonary syndrome (ICD-11 hantavirus disease subcode 1D62.1) [30,85]. Unclassified orthohantaviruses associated with HPS are several ANDV-like viruses (e.g., “Araraquara”, “Araucária”, “Bermejo”, “Juquitiba”, “Maciel”, “Paranoá virus”, “Pergamino”, and “Tunari”), “Anajatuba virus” and the SNV-like viruses (“Blue River” and “Monongahela”) [85]. * Robina virus might be a mobatvirus, possibly requiring reclassification [72].

5. Evolution of Hantavirids

After the genus Hantavirus was established, the idea that each hantavirus was uniquely adapted to a particular, distinct host and that these viruses co-evolved (co-speciated) with their hosts began to take shape [86,87]. The four best-characterized hantaviruses at the time were observed to persistently infect specific/distinct rodent hosts without causing discernible disease: HTNV was known to be hosted by murid striped field mice [17,18,19], PHV by cricetid meadow voles (Microtus (Mynomes) pennsylvanicus (Ord, 1815)) [53], PUUV by cricetid bank voles (Clethrionomys glareolus (Schreber, 1780)) [88], and SEOV by murid brown rats (Rattus norvegicus (Berkenhout, 1769)) and roof rats (Rattus rattus (Linnaeus, 1758)) [89,90], respectively. This close association of one particular hantavirus with one particular rodent host on largely overlapping virus/rodent phylogenetic trees became a frequently repeated pattern, and ultimately a dogma. However, from the beginning, this dogma was not supported scientifically in absolute terms; for example, as outlined above, SEOV was already known to infect at least two specific rodents [89]. The already-mentioned susceptibility of various distinct deermice to SNV infection, recognized only after the taxonomy of deermice had to be revised based on molecular evidence [38,39,40], further emphasizes that the natural virus–host connections are not yet well-defined. Even a further relaxed interpretation of co-evolution (i.e., a dogma loosened to virus–host genus association) was challenged: A serologically distinct hantavirus, Dobrava virus (DOBV), was discovered in yellow-necked field mice (Apodemus flavicollis (Melchior, 1834)) [91,92,93], i.e., in a different species of Apodemus than that harboring HTNV. To stick to the overall idea, TPMV, the virus discovered in soricid shrews [46], had to be ignored or the shrew host had to be explained as a spillover host from an unidentified “true” rodent host. However, after 2007 [50,61,62,63,64], eulipotyphlan hantaviruses could not be ignored anymore.
As exceptions to the one-mammal-one-hantavirus rule became more frequent than the rule itself [94,95], it became apparent that hantavirid co-speciation with hosts is just one factor that influenced hantavirid evolution. Genomic segment reassortment among hantavirids [96], host spillover, and host-switching [97,98,99,100,101,102] have likely occurred many times and obfuscated the evolutionary history of the family Hantaviridae. Various theories on hantavirid evolution have been discussed over recent decades [86,87,103,104,105,106,107,108,109,110,111,112,113]. However, none of them included the recently discovered acanthavirins, agantavirins, and repantavirins, rendering them ineffective for the entire family. Mammantavirins (loanviruses, mobatviruses, orthohantaviruses, and thottimviruses) offer themselves to a cohesive analysis because they, at least according to current knowledge, exclusively infect mammals. Their broad infection of bats, eulipotyphlans, and rodents would require the mammantavirin ancestor to be a virus of an early boreoeutherian, i.e., an animal that existed at the estimated diversification point of placental mammals in the Cenozoic (≈66 My ago). However, this assumption may be challenged soon, as accumulating evidence alludes to the existence of marsupial orthohantaviruses [69]. If virus–host co-evolution/co-speciation is a baseline assumption, then inclusion of acanthavirins, agantavirins, and repantavirins moves the hantavirid ancestor at least to the rise of jawless fish, i.e., around or before the Late Carboniferous (≈359–299 My ago). However, this hypothesis brings up the challenging question of why hantavirids were only found in a few animal clades rather than in all of them, assuming that they have not simply been massively undersampled.
An alternative hypothesis is that the hantavirid phylogeny is the result of a more recent history, possibly resulting from preferential host-switching and local adaptation rather than parallel host and virus evolution. Evidence supporting this hypothesis includes the finding of specific hantavirids in more than one specific host and the absence of hantavirids in many hosts. Of course, this hypothesis would not explain the origin of mammalian hantavirids, but the origin of bunyavirals [114] suggests ecdysozoans (e.g., arthropods such as insects or arachnids) as early or even current hantavirid hosts. Fitting the latter (heretical) hypothesis are the recent reports of hantavirid-related RNA-directed RNA polymerase-encoding nucleic acids, found by metagenomic sequencing in curculionid diaprepes root weevils (“coleopteran hanta-related virus OKIAV221”) and a perlid stonefly (“plecopteran hanta-related virus OKIAV215”) [115].

6. Discussion and Future Directions

So, what is a hantavirid? For now, the answer has become rather unsatisfactory: Hantavirids form a distinct clade of animal-infecting cluster 1 bunyavirals that are closely related to viruses assigned to families Arenaviridae, Cruliviridae, Fimoviridae, Phasmaviridae, Peribunyaviridae, and Tospoviridae [116]. Their evolutionary history is unclear and will likely not be resolved until targeted studies increase confidence in the overall spectrum of hantavirid hosts. The thus-far sporadic discoveries of hantavirids in highly diverse (actinpterygiid and myxinid) fish and (gekkotan and scincomorphan) reptiles [74,75,76,77,78] indicate enormous diversity and imply that hantavirids infect amphibians and possibly crocodilians and their closest relatives, i.e., birds. The latter possibility is supported by at least one publication [117]. The history of the long-ignored soricid TPMV is a reminder that such anecdotal evidence should not be discounted until disproven.
While these larger questions are explored, hantavirologists will also have to increase the resolution of established taxonomies. The genomes of numerous hantavirids (several of which are shown in this review in quotation marks) and the genomes of dozens of “classic” rodent orthohantaviruses have not been completely sequenced. This lack of data not only prevents their official classification [80] but also prevents honing in on such pressing issues as understanding the role of genomic segment reassortment in hantavirid evolution or defining species and species complexes in hantavirid taxonomy. On the host side, recent developments indicate that even the taxonomy of rodents is much less certain than previously thought. With entire genera, such as Peromyscus, being reorganized based on molecular evidence [39], the true hantavirid–host relationships will likely have to be re-evaluated entirely. It is possible that these efforts will allow the reestablishment of some prior dogmas, such as the one-hantavirid-one-host hypothesis or the notion that members of individual hantavirid subfamilies only infect particular animal groups (fish, reptiles, or mammals). Alternatively, re-evaluation may require abandonment of any of these as obsolete. Today, only one dogma of yore still stands: All hantaviruses known to cause disease in humans are rodent-borne.

Author Contributions

Conceptualization, J.H.K. and C.S.S.; writing—original draft preparation, J.H.K. and C.S.S.; writing—review and editing, J.H.K. and C.S.S. All authors have read and agreed to the published version of the manuscript.


This work was supported in part through Laulima Government Solutions, LLC, prime contract with the National Institutes of Health (NIH) and the National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Government Solutions, LLC, under Contract No. HHSN272201800013C.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.


The authors thank Anya Crane (Integrated Research Facility at Fort Detrick/Division of Clinical Research/National Institute of Allergy and Infectious Diseases/National Institutes of Health, Fort Detrick, Frederick, MD, USA) for critically editing the manuscript.

Conflicts of Interest

The authors declare no conflict of interest.


  1. LeDuc, J.W.; Childs, J.E.; Glass, G.E. The hantaviruses, etiologic agents of hemorrhagic fever with renal syndrome: A possible cause of hypertension and chronic renal disease in the United States. Annu. Rev. Public Health 1992, 13, 79–98. [Google Scholar] [CrossRef]
  2. Schmaljohn, C.S.; Hasty, S.E.; Harrison, S.A.; Dalrymple, J.M. Characterization of Hantaan virions, the prototype virus of hemorrhagic fever with renal syndrome. J. Infect. Dis. 1983, 148, 1005–1012. [Google Scholar] [CrossRef]
  3. Schmaljohn, C.S.; Hasty, S.E.; Dalrymple, J.M. Antigenic and molecular properties of eight viruses in the newly proposed Hantavirus genus of Bunyaviridae. Arthropod Borne Virus Inf. Exch. 1984, 158–159. [Google Scholar]
  4. Schmaljohn, C.S.; Dalrymple, J.M. Analysis of Hantaan virus RNA: Evidence for a new genus of Bunyaviridae. Virology 1983, 131, 482–491. [Google Scholar] [CrossRef] [PubMed]
  5. Francki, R.I.B.; Fauquet, C.M.; Knudson, D.L.; Brown, F. Genus Hantavirus. In Classification and Nomenclature of Viruses. Fifth Report of the International Committee on Taxonomy of Viruses. Archives of Virology Supplement, Volume 2; Springer: Vienna, Austria, 1991. [Google Scholar]
  6. International Committee on Taxonomy of Viruses. Taxon Details. Genus: Orthohantavirus. 1987 Plenary Session Vote 12 August 1987 in Edmonton (MSL #10). 2022. Available online: (accessed on 22 February 2023).
  7. Hughes, J.M.; Peters, C.J.; Cohen, M.L.; Mahy, B.W.J. Hantavirus pulmonary syndrome: An emerging infectious disease. Science 1993, 262, 850–851. [Google Scholar] [CrossRef]
  8. Nichol, S.T.; Spiropoulou, C.F.; Morzunov, S.; Rollin, P.E.; Ksiazek, T.G.; Feldmann, H.; Sanchez, A.; Childs, J.; Zaki, S.; Peters, C.J. Genetic identification of a hantavirus associated with an outbreak of acute respiratory illness. Science 1993, 262, 914–917. [Google Scholar] [CrossRef]
  9. Maes, P.; Alkhovsky, S.V.; Bào, Y.; Beer, M.; Birkhead, M.; Briese, T.; Buchmeier, M.J.; Calisher, C.H.; Charrel, R.N.; Choi, I.R.; et al. Taxonomy of the family Arenaviridae and the order Bunyavirales: Update 2018. Arch. Virol. 2018, 163, 2295–2310. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  10. Jellison, W.L.; Owen, C.R. Korean hemorrhagic fever. In Diseases Transmitted from Animals to Man; Hull, T.G., Ed.; Charles, C. Thomas: Springfield, IL, USA, 1963; pp. 813–822. [Google Scholar]
  11. Smadel, J.E. Epidemic hemorrhagic fever. Am. J. Public Health Nations Health 1953, 43, 1327–1330. [Google Scholar] [CrossRef] [Green Version]
  12. Lee, H.W. Korean hemorrhagic fever. Prog. Med. Virol. 1982, 28, 96–113. [Google Scholar]
  13. Abercrombie, R.G. Observations on the acute phase of five hundred cases of war nephritis. J. R. Army Med. Corps 1916, XXVII, 131–157. [Google Scholar]
  14. Bradford, J.R. Nephritis in the British troops in Flanders. A preliminary note. Q. J. Med. 1916, 9, 125–137. [Google Scholar] [CrossRef] [Green Version]
  15. Brown, W.L. Trench nephritis. Lancet 1916, 187, 391–395. [Google Scholar] [CrossRef]
  16. Gajdusek, D.C. Das epidemische hämorrhagische Fieber. Klin. Wochenschr 1956, 34, 769–777. [Google Scholar] [CrossRef] [PubMed]
  17. Lee, H.W.; Lee, P.W.; Johnson, K.M. Isolation of the etiologic agent of Korean Hemorrhagic fever. J. Infect. Dis. 1978, 137, 298–308. [Google Scholar] [CrossRef] [PubMed]
  18. 李鎬汪; 李平佑. 韓國型 出血热-I. 原因 抗原 및 抗體 證明. 대한내파학회장지 1976, 19, 371–383. [Google Scholar]
  19. 李鎬汪; 李平佑. 韓國型 出血热-II. 病原體 分离. 大韓바이러스學會誌 1977, 7, 19–29. [Google Scholar]
  20. French, G.R.; Foulke, R.S.; Brand, O.A.; Eddy, G.A.; Lee, H.W.; Lee, P.W. Korean hemorrhagic fever: Propagation of the etiologic agent in a cell line of human origin. Science 1981, 211, 1046–1048. [Google Scholar] [CrossRef]
  21. McCormick, J.B.; Palmer, E.L.; Sasso, D.R.; Kiley, M.P. Morphological identification of the agent of Korean haemorrhagic fever (Hantaan virus) as a member of the Bunyaviridae. Lancet 1982, 319, 765–768. [Google Scholar] [CrossRef]
  22. White, J.D.; Shirey, F.G.; French, G.R.; Huggins, J.W.; Brand, O.M.; Lee, H.W. Hantaan virus, aetiological agent of Korean haemorrhagic fever, has Bunyaviridae-like morphology. Lancet 1982, 319, 768–771. [Google Scholar] [CrossRef] [PubMed]
  23. Lee, H.W.; Lee, P.W.; Lähdevirta, J.; Brummer-Korventkontio, M. Ætiological relation between Korean hæmorrhagic fever and nephropathia epidemica. Lancet 1979, 313, 186–187. [Google Scholar]
  24. Lee, H.W.; Lee, P.W.; Tamura, M.; Tamura, T.; Okuno, Y. Etiological relation between Korean hemorrhagic fever and epidemic hemorrhagic fever in Japan. Biken J. 1979, 22, 41–45. [Google Scholar]
  25. Lee, P.W.; Gajdusek, D.C.; Gibbs, C.J.; Xu, Z.-Y. Ætiological relation between Korean hæmorrhagic fever with renal syndrome in People’s Republic of China. Lancet 1980, 315, 819–820. [Google Scholar] [CrossRef]
  26. Svedmyr, A.; Lee, H.W.; Berglund, A.; Hoorn, B.; Nyström, K.; Gajdusek, D.C. Epidemic nephropathy in Scandinavia is related to Korean hæmorrhagic fever. Lancet 1979, 313, 100. [Google Scholar] [CrossRef]
  27. Svedmyr, A.; Lee, P.W.; Gajdusek, D.C.; Gibbs, C.J., Jr.; Nyström, K. Antigenic differentiation of the viruses causing Korean hæmorrhagic fever and epidemic (endemic) nephropathy of Scandinavia. Lancet 1980, 316, 315–316. [Google Scholar] [CrossRef]
  28. Gajdusek, D.C.; Goldgaber, D.; Millard, E. Bibliography of Hemorrhagic Fever with Renal Syndrome (Muroid virus Nephropathy). National Institutes of Health Publication No. 83-2603; US Department of Health and Human Services, Public Health Service, National Institutes of Health: Bethesda, ML, USA, 1983. [Google Scholar]
  29. World Health Organization. Report of the Working Group on Haemorrhagic Fever with Renal Syndrome, Tokyo, Japan, February 22–24 1982. Document number (WP) CRP/ICP/BVM/012, WPR/RPD/WG/(HFRS)/82.16. 1982. Available online: (accessed on 22 February 2023).
  30. World Health Organization. ICD-11. International Classification of Diseases 11th Revision. 2022. Available online: (accessed on 22 February 2023).
  31. Schmaljohn, C.S.; Hasty, S.E.; Rasmussen, L.; Dalrymple, J.M. Hantaan virus replication: Effects of monensin, tunicamycin and endoglycosidases on the structural glycoproteins. J. Gen. Virol. 1986, 67 Pt 4, 707–717. [Google Scholar] [CrossRef] [PubMed]
  32. Schmaljohn, C.S.; Jennings, G.B.; Hay, J.; Dalrymple, J.M. Coding strategy of the S genome segment of Hantaan virus. Virology 1986, 155, 633–643. [Google Scholar] [CrossRef] [PubMed]
  33. Schmaljohn, C.S.; Hasty, S.E.; Dalrymple, J.M.; LeDuc, J.W.; Lee, H.W.; von Bonsdorff, C.-H.; Brummer-Korvenkontio, M.; Vaheri, A.; Tsai, T.F.; Regnery, H.L.; et al. Antigenic and genetic properties of viruses linked to hemorrhagic fever with renal syndrome. Science 1985, 227, 1041–1044. [Google Scholar] [CrossRef]
  34. Centers for Disease Control and Prevention. Outbreak of acute illness -- Southwestern United States, 1993. MMWR. Morb. Mortal. Wkly. Rep. 1993, 42, 421–424. [Google Scholar]
  35. Hjelle, B.; Jenison, S.; Torrez-Martinez, N.; Yamada, T.; Nolte, K.; Zumwalt, R.; MacInnes, K.; Myers, G. A novel hantavirus associated with an outbreak of fatal respiratory disease in the southwestern United States: Evolutionary relationships to known hantaviruses. J. Virol. 1994, 68, 592–596. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Jenison, S.; Yamada, T.; Morris, C.; Anderson, B.; Torrez-Martinez, N.; Keller, N.; Hjelle, B. Characterization of human antibody responses to four corners hantavirus infections among patients with hantavirus pulmonary syndrome. J. Virol. 1994, 68, 3000–3006. [Google Scholar] [CrossRef] [Green Version]
  37. Frampton, J.W.; Lanser, S.; Nichols, C.R.; Ettestad, P.J. Sin Nombre virus infection in 1959. Lancet 1995, 346, 781–782. [Google Scholar] [CrossRef] [PubMed]
  38. Childs, J.E.; Ksiazek, T.G.; Spiropoulou, C.F.; Krebs, J.W.; Morzunov, S.; Maupin, G.O.; Gage, K.L.; Rollin, P.E.; Sarisky, J.; Enscore, R.E.; et al. Serologic and genetic identification of Peromyscus maniculatus as the primary rodent reservoir for a new hantavirus in the southwestern United States. J. Infect. Dis. 1994, 169, 1271–1280. [Google Scholar] [CrossRef] [Green Version]
  39. Greenbaum, I.F.; Honeycutt, R.L.; Chirhart, S.E. Taxonomy and phylogenetics of the Peromyscus maniculatus species group. In From Field to Laboratory: A Memorial Volume in Honor of Robert J. Baker; Bradley, R.D., Genoways, H.H., Schmidley, D.J., Bradley, L.C., Eds.; Special Publications, Museum of Texas Tech University: Lubbock, TX, USA, 2019; Volume 71, pp. 559–575. [Google Scholar]
  40. Quizon, K.; Holloway, K.; Iranpour, M.; Warner, B.M.; Deschambault, Y.; Soule, G.; Tierney, K.; Kobasa, D.; Sloan, A.; Safronetz, D. Experimental infection of Peromyscus species rodents with Sin Nombre virus. Emerg. Infect. Dis. 2022, 28, 1882–1885. [Google Scholar] [CrossRef] [PubMed]
  41. Alonso, D.O.; Iglesias, A.; Coelho, R.; Periolo, N.; Bruno, A.; Córdoba, M.T.; Filomarino, N.; Quipildor, M.; Biondo, E.; Fortunato, E.; et al. Epidemiological description, case-fatality rate, and trends of hantavirus pulmonary syndrome: 9 years of surveillance in Argentina. J. Med. Virol. 2019, 91, 1173–1181. [Google Scholar] [CrossRef] [PubMed]
  42. Enria, D.; Padula, P.; Segura, E.L.; Pini, N.; Edelstein, A.; Posse, C.R.; Weissenbacher, M.C. Hantavirus pulmonary syndrome in Argentina. Possibility of person to person transmission. Medicina 1996, 56, 709–711. [Google Scholar]
  43. Martinez, V.P.; Bellomo, C.M.; Cacace, M.L.; Suárez, P.; Bogni, L.; Padula, P.J. Hantavirus pulmonary syndrome in Argentina, 1995–2008. Emerg. Infect. Dis. 2010, 16, 1853–1860. [Google Scholar] [CrossRef]
  44. Martínez, V.P.; Di Paola, N.; Alonso, D.O.; Pérez-Sautu, U.; Bellomo, C.M.; Iglesias, A.A.; Coelho, R.M.; López, B.; Periolo, N.; Larson, P.A.; et al. “Super-spreaders” and person-to-person transmission of Andes virus in Argentina. N. Engl. J. Med. 2020, 383, 2230–2241. [Google Scholar] [CrossRef]
  45. Riquelme, R.; Rioseco, M.L.; Bastidas, L.; Trincado, D.; Riquelme, M.; Loyola, H.; Valdivieso, F. Hantavirus pulmonary syndrome, Southern Chile, 1995–2012. Emerg. Infect. Dis. 2015, 21, 562–568. [Google Scholar] [CrossRef] [Green Version]
  46. Carey, D.E.; Reuben, R.; Panicker, K.N.; Shope, R.E.; Myers, R.M. Thottapalayam virus: A presumptive arbovirus isolated from a shrew in India. Indian J. Med. Res. 1971, 59, 1758–1760. [Google Scholar]
  47. Chu, Y.K.; Rossi, C.; LeDuc, J.W.; Lee, H.W.; Schmaljohn, C.S.; Dalrymple, J.M. Serological relationships among viruses in the Hantavirus genus, family Bunyaviridae. Virology 1994, 198, 196–204. [Google Scholar] [CrossRef]
  48. Xiao, S.-Y.; LeDuc, J.W.; Chu, Y.K.; Schmaljohn, C.S. Phylogenetic analyses of virus isolates in the genus Hantavirus, family Bunyaviridae. Virology 1994, 198, 205–217. [Google Scholar] [CrossRef] [PubMed]
  49. Zeller, H.G.; Karabatsos, N.; Calisher, C.H.; Digoutte, J.-P.; Cropp, C.B.; Murphy, F.A.; Shope, R.E. Electron microscopic and antigenic studies of uncharacterized viruses. II. Evidence suggesting the placement of viruses in the family Bunyaviridae. Arch. Virol. 1989, 108, 211–227. [Google Scholar] [CrossRef] [PubMed]
  50. Song, J.-W.; Baek, L.J.; Schmaljohn, C.S.; Yanagihara, R. Thottapalayam virus, a prototype shrewborne hantavirus. Emerg. Infect. Dis. 2007, 13, 980–985. [Google Scholar] [CrossRef]
  51. Gavrilovskaya, I.N.; Apekina, N.S.; Myasnikov, Y.A.; Bernshtein, A.D.; Ryltseva, E.V.; Gorbachkova, E.A.; Chumakov, M.P. Features of circulation of hemorrhagic fever with renal syndrome (HFRS) virus among small mammals in the European U.S.S.R. Arch. Virol. 1983, 75, 313–316. [Google Scholar] [CrossRef]
  52. Gligic, A.; Stojanovic, R.; Obradovic, M.; Hlaca, D.; Dimkovic, N.; Diglisic, G.; Lukac, V.; Ler, Z.; Bogdanovic, R.; Antonijevic, B.; et al. Hemorrhagic fever with renal syndrome in Yugoslavia: Epidemiologic and epizootiologic features of a nationwide outbreak in 1989. Eur. J. Epidemiol. 1992, 8, 816–825. [Google Scholar] [CrossRef] [PubMed]
  53. Lee, P.-W.; Amyx, H.L.; Yanagihara, R.; Gajdusek, D.C.; Goldgaber, D.; Gibbs, C.J., Jr. Partial characterization of Prospect Hill virus isolated from meadow voles in the United States. J. Infect. Dis. 1985, 152, 826–829. [Google Scholar] [CrossRef]
  54. Tang, Y.W.; Ruo, S.L.; Xu, X.; Sanchez, A.; Fisher-Hoch, S.P.; McCormick, J.B.; Xu, Z.Y. Hantavirus strains isolated from rodentia and insectivora in rural China differentiated by polymerase chain reaction assay. Arch. Virol. 1990, 115, 37–46. [Google Scholar] [CrossRef] [PubMed]
  55. Tang, Y.W.; Xu, Z.Y.; Zhu, Z.Y.; Tsai, T.F. Isolation of haemorrhagic fever with renal syndrome virus from Suncus murinus, an insectivore. Lancet 1985, 325, 513–514. [Google Scholar] [CrossRef]
  56. Tkachenko, E.A.; Ivanov, A.P.; Donets, M.A.; Miasnikov, Y.A.; Ryltseva, E.V.; Gaponova, L.K.; Bashkirtsev, V.N.; Okulova, N.M.; Drozdov, S.G.; Slonova, R.A.; et al. Potential reservoir and vectors of haemorrhagic fever with renal syndrome (HFRS) in the U. S. S. R. Ann. Soc. Belg. Med. Trop. 1983, 63, 267–269. [Google Scholar]
  57. Tsai, T.F.; Tang, Y.W.; Hu, S.L.; Ye, K.L.; Chen, G.L.; Xu, Z.Y. Hemagglutination-inhibiting antibody in hemorrhagic fever with renal syndrome. J. Infect. Dis. 1984, 150, 895–898. [Google Scholar] [CrossRef]
  58. Yan, D.Y.; Xie, Y.J.; Zhang, C.A.; McCormick, J.B.; Sanchez, A.; Engelman, H.M.; Chen, S.Z.; Gu, X.S.; Tang, W.T.; Zhang, J. New isolates of HFRS virus in Sichuan, China and characterisation of antigenic differences by monoclonal antibodies. Lancet 1986, 328, 1328. [Google Scholar] [CrossRef] [PubMed]
  59. Ткаченкo, Е.А.; Рыльцева, Е.В.; Мясникoв, Ю.А.; Иванoв, А.П.; Резапкин, Г.В. Изучение циркуляции вируса гемoррагическoй лихoрадки с пoчечным синдрoмoм среди мелких млекoпитающих на территoрии СССР. Вoпр Вирусoл 1987, 32, 709–715. [Google Scholar]
  60. 陈尚智; 陈立礼; 陶国方; 傅建林; 张传安; 吴应涛; 罗梁娟; 王酉之. 从中麝鼩和四川短尾鼩分离到流行性出血热病毒. 中华预防医学杂志 1986, 20, 261–263. [Google Scholar]
  61. Song, J.-W.; Gu, S.H.; Bennett, S.N.; Arai, S.; Puorger, M.; Hilbe, M.; Yanagihara, R. Seewis virus, a genetically distinct hantavirus in the Eurasian common shrew (Sorex araneus). Virol. J. 2007, 4, 114. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  62. Arai, S.; Song, J.-W.; Sumibcay, L.; Bennett, S.N.; Nerurkar, V.R.; Parmenter, C.; Cook, J.A.; Yates, T.L.; Yanagihara, R. Hantavirus in northern short-tailed shrew, United States. Emerg. Infect. Dis. 2007, 13, 1420–1423. [Google Scholar] [CrossRef] [PubMed]
  63. Song, J.-W.; Kang, H.J.; Song, K.-J.; Truong, T.T.; Bennett, S.N.; Arai, S.; Truong, N.U.; Yanagihara, R. Newfound hantavirus in Chinese mole shrew, Vietnam. Emerg. Infect. Dis. 2007, 13, 1784–1787. [Google Scholar] [CrossRef]
  64. Klempa, B.; Fichet-Calvet, E.; Lecompte, E.; Auste, B.; Aniskin, V.; Meisel, H.; Barrière, P.; Koivogui, L.; ter Meulen, J.; Krüger, D.H. Novel hantavirus sequences in Shrew, Guinea. Emerg. Infect. Dis. 2007, 13, 520–522. [Google Scholar] [CrossRef]
  65. Arai, S.; Yanagihara, R. Genetic diversity and geographic distribution of bat-borne hantaviruses. Curr. Issues Mol. Biol. 2020, 39, 1–28. [Google Scholar] [CrossRef]
  66. Arai, S.; Ohdachi, S.D.; Asakawa, M.; Kang, H.J.; Mocz, G.; Arikawa, J.; Okabe, N.; Yanagihara, R. Molecular phylogeny of a newfound hantavirus in the Japanese shrew mole (Urotrichus talpoides). Proc. Natl. Acad. Sci. USA 2008, 105, 16296–16301. [Google Scholar] [CrossRef] [Green Version]
  67. Yashina, L.N.; Panov, V.V.; Abramov, S.A.; Smetannikova, N.A.; Luchnikova, E.M.; Dupal, T.A.; Krivopalov, A.V.; Arai, S.; Yanagihara, R. Academ Virus, a novel hantavirus in the Siberian mole (Talpa altaica) from Russia. Viruses 2022, 14, 309. [Google Scholar] [CrossRef]
  68. Hugot, J.-P.; Vanmechelen, B.; Maes, P. Landiras virus, a novel hantavirus hosted by Talpa aquitina n.sp, a recently disocvered south European mole species. Bull. Acad. Vét. Fr. 2023. [Google Scholar] [CrossRef]
  69. de Araujo, J.; Thomazelli, L.M.; Henriques, D.A.; Lautenschalager, D.; Ometto, T.; Dutra, L.M.; Aires, C.C.; Favorito, S.; Durigon, E.L. Detection of hantavirus in bats from remaining rain forest in São Paulo, Brazil. BMC Res. Notes 2012, 5, 690. [Google Scholar] [CrossRef] [Green Version]
  70. Kim, G.R.; Lee, Y.T.; Park, C.H. A new natural reservoir of hantavirus: Isolation of hantaviruses from lung tissues of bats. Arch. Virol. 1994, 134, 85–95. [Google Scholar] [CrossRef]
  71. Weiss, S.; Witkowski, P.T.; Auste, B.; Nowak, K.; Weber, N.; Fahr, J.; Mombouli, J.-V.; Wolfe, N.D.; Drexler, J.F.; Drosten, C.; et al. Hantavirus in bat, Sierra Leone. Emerg. Infect. Dis. 2012, 18, 159–161. [Google Scholar] [CrossRef] [PubMed]
  72. Weiss, S.; Sudi, L.E.; Düx, A.; Mangu, C.D.; Ntinginya, N.E.; Shirima, G.M.; Köndgen, S.; Schubert, G.; Witkowski, P.T.; Muyembe, J.J.; et al. Kiwira Virus, a newfound hantavirus discovered in free-tailed bats (Molossidae) in East and Central Africa. Viruses 2022, 14, 2368. [Google Scholar] [CrossRef] [PubMed]
  73. Zana, B.; Kemenesi, G.; Buzás, D.; Csorba, G.; Görföl, T.; Khan, F.A.A.; Tahir, N.F.D.A.; Zeghbib, S.; Madai, M.; Papp, H.; et al. Molecular identification of a novel hantavirus in Malaysian bronze tube-nosed bats (Murina aenea). Viruses 2019, 11, 887. [Google Scholar] [CrossRef] [Green Version]
  74. Hierweger, M.M.; Koch, M.C.; Rupp, M.; Maes, P.; Di Paola, N.; Bruggmann, R.; Kuhn, J.H.; Schmidt-Posthaus, H.; Seuberlich, T. Novel filoviruses, hantavirus, and rhabdovirus in freshwater fish, Switzerland, 2017. Emerg. Infect. Dis. 2021, 27, 3082–3091. [Google Scholar] [CrossRef]
  75. Shi, M.; Lin, X.-D.; Chen, X.; Tian, J.-H.; Chen, L.-J.; Li, K.; Wang, W.; Eden, J.-S.; Shen, J.-J.; Liu, L.; et al. The evolutionary history of vertebrate RNA viruses. Nature 2018, 556, 197–202. [Google Scholar] [CrossRef]
  76. Costa, V.A.; Mifsud, J.C.O.; Gilligan, D.; Williamson, J.E.; Holmes, E.C.; Geoghegan, J.L. Metagenomic sequencing reveals a lack of virus exchange between native and invasive freshwater fish across the Murray-Darling Basin, Australia. Virus Evol. 2021, 7, veab034. [Google Scholar] [CrossRef] [PubMed]
  77. Geoghegan, J.L.; Di Giallonardo, F.; Wille, M.; Ortiz-Baez, A.S.; Costa, V.A.; Ghaly, T.; Mifsud, J.C.O.; Turnbull, O.M.H.; Bellwood, D.R.; Williamson, J.E.; et al. Virome composition in marine fish revealed by meta-transcriptomics. Virus Evol. 2021, 7, veab005. [Google Scholar] [CrossRef]
  78. Harding, E.F.; Russo, A.G.; Yan, G.J.H.; Mercer, L.K.; White, P.A. Revealing the uncharacterised diversity of amphibian and reptile viruses. ISME Commun. 2022, 2, 95. [Google Scholar] [CrossRef]
  79. Vetten, H.J.; Haenni, A.-L. Taxon-specific suffixes for vernacular names. Arch. Virol. 2006, 151, 1249–1250. [Google Scholar] [CrossRef]
  80. Laenen, L.; Vergote, V.; Calisher, C.H.; Klempa, B.; Klingström, J.; Kuhn, J.H.; Maes, P. Hantaviridae: Current classification and future perspectives. Viruses 2019, 11, 788. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  81. Maes, P.; Adkins, S.; Alkhovsky, S.V.; Avšič-Županc, T.; Ballinger, M.J.; Bente, D.A.; Beer, M.; Bergeron, É.; Blair, C.D.; Briese, T.; et al. Taxonomy of the order Bunyavirales: Second update 2018. Arch. Virol. 2019, 164, 927–941. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  82. Abudurexiti, A.; Adkins, S.; Alioto, D.; Alkhovsky, S.V.; Avšič-Županc, T.; Ballinger, M.J.; Bente, D.A.; Beer, M.; Bergeron, É.; Blair, C.D.; et al. Taxonomy of the order Bunyavirales: Update 2019. Arch. Virol. 2019, 164, 1949–1965. [Google Scholar] [CrossRef] [Green Version]
  83. Kuhn, J.H.; Adkins, S.; Alkhovsky, S.V.; Avšič-Županc, T.; Ayllón, M.A.; Bahl, J.; Balkema-Buschmann, A.; Ballinger, M.J.; Bandte, M.; Beer, M.; et al. 2022 taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales. Arch. Virol. 2022, 167, 2857–2906. [Google Scholar] [CrossRef]
  84. Postler, T.S.; Bradfute, S.B.; Calisher, C.H.; Klingström, J.; Laenen, L.; Maes, P.; Kuhn, J.H. Rename all Species in the Family to Comply with the ICTV-Mandated Binomial Format (Bunyavirales: Hantaviridae). International Committee for Taxonomy of Viruses Proposal (Taxoprop) No. 2021.013M. 2022. Available online: (accessed on 22 February 2023).
  85. Kuhn, J.H.; Crozier, I. Arthropod-borne and rodent-borne virus infections. In Harrison’s Principles of Internal Medicine, 21st ed.; Loscalzo, J., Fauci, A.S., Kasper, D.L., Hauser, S.L., Longo, D.L., Jameson, J.L., Eds.; McGraw-Hill Education: Columbus, OH, USA, 2022; Volume 2, pp. 1624–1645. [Google Scholar]
  86. Plyusnin, A.; Vapalahti, O.; Vaheri, A. Hantaviruses: Genome structure, expression and evolution. J. Gen. Virol. 1996, 77 Pt 11, 2677–2687. [Google Scholar] [CrossRef]
  87. Zhao, X.; Hay, J. The evolution of hantaviruses. Immunol. Investig. 1997, 26, 191–197. [Google Scholar] [CrossRef]
  88. Yanagihara, R.; Goldgaber, D.; Lee, P.-W.; Amyx, H.L.; Gajdusek, D.C.; Gibbs, C.J., Jr.; Svedmyr, A. Propagation of nephropathia epidemica virus in cell culture. Lancet 1984, 323, 1013. [Google Scholar] [CrossRef]
  89. Lee, H.W.; Baek, L.J.; Johnson, K.M. Isolation of Hantaan virus, the etiologic agent of Korean hemorrhagic fever, from wild urban rats. J. Infect. Dis. 1982, 146, 638–644. [Google Scholar] [CrossRef]
  90. 宋干; 杭长寿; 廖化新; 裘学昭; 高广忠; 杜永林; 赵君能; 徐剑锟; 孔碧霞. 从轻型出血热疫区的褐家鼠分离到与流行性出血热有关的病原因子. 微生物学报 1982, 22, 373–377. [Google Scholar]
  91. Avsic-Zupanc, T.; Toney, A.; Anderson, K.; Chu, Y.-K.; Schmaljohn, C. Genetic and antigenic properties of Dobrava virus: A unique member of the Hantavirus genus, family Bunyaviridae. J. Gen. Virol. 1995, 76 Pt 11, 2801–2808. [Google Scholar] [CrossRef]
  92. Avsic-Zupanc, T.; Xiao, S.-Y.; Stojanovic, R.; Gligic, A.; van der Groen, G.; LeDuc, J.W. Characterization of Dobrava virus: A Hantavirus from Slovenia, Yugoslavia. J. Med. Virol. 1992, 38, 132–137. [Google Scholar] [CrossRef]
  93. Xiao, S.-Y.; Diglisic, G.; Avsic-Zupanc, T.; LeDuc, J.W. Dobrava virus as a new hantavirus: Evidenced by comparative sequence analysis. J. Med. Virol. 1993, 39, 152–155. [Google Scholar] [CrossRef]
  94. Kikuchi, F.; Senoo, K.; Arai, S.; Tsuchiya, K.; Sơn, N.T.; Motokawa, M.; Ranorosoa, M.C.; Bawm, S.; Lin, K.S.; Suzuki, H.; et al. Rodent-borne orthohantaviruses in Vietnam, Madagascar and Japan. Viruses 2021, 13, 1343. [Google Scholar] [CrossRef] [PubMed]
  95. Mull, N.; Jackson, R.; Sironen, T.; Forbes, K.M. Ecology of neglected rodent-borne American orthohantaviruses. Pathogens 2020, 9, 325. [Google Scholar] [CrossRef] [PubMed]
  96. Klempa, B. Reassortment events in the evolution of hantaviruses. Virus Genes 2018, 54, 638–646. [Google Scholar] [CrossRef] [Green Version]
  97. Guo, W.-P.; Lin, X.-D.; Wang, W.; Tian, J.-H.; Cong, M.-L.; Zhang, H.-L.; Wang, M.-R.; Zhou, R.-H.; Wang, J.-B.; Li, M.-H.; et al. Phylogeny and origins of hantaviruses harbored by bats, insectivores, and rodents. PLoS Pathog. 2013, 9, e1003159. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  98. Klingström, J.; Heyman, P.; Escutenaire, S.; Sjölander, K.B.; De Jaegere, F.; Henttonen, H.; Lundkvist, Å. Rodent host specificity of European hantaviruses: Evidence of Puumala virus interspecific spillover. J. Med. Virol. 2002, 68, 581–588. [Google Scholar] [CrossRef]
  99. Kouadio, L.; Nowak, K.; Couacy-Hymann, E.; Akoua-Koffi, C.; Düx, A.; Zimmermann, F.; Allali, B.K.; Kourouma, L.; Bangoura, K.; Koendgen, S.; et al. Detection of possible spillover of a novel hantavirus in a Natal mastomys from Guinea. Virus Genes 2020, 56, 95–98. [Google Scholar] [CrossRef]
  100. Liphardt, S.W.; Kang, H.J.; Dizney, L.J.; Ruedas, L.A.; Cook, J.A.; Yanagihara, R. Complex history of codiversification and host switching of a newfound soricid-borne orthohantavirus in North America. Viruses 2019, 11, 637. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  101. Nemirov, K.; Henttonen, H.; Vaheri, A.; Plyusnin, A. Phylogenetic evidence for host switching in the evolution of hantaviruses carried by Apodemus mice. Virus Res. 2002, 90, 207–215. [Google Scholar] [CrossRef] [PubMed]
  102. Wang, W.; Wang, M.-R.; Lin, X.-D.; Guo, W.-P.; Li, M.-H.; Mei, S.-H.; Li, Z.-M.; Cong, M.-L.; Jiang, R.-L.; Zhou, R.-H.; et al. Ongoing spillover of Hantaan and gou hantaviruses from rodents is associated with hemorrhagic fever with renal syndrome (HFRS) in China. PLoS Negl. Trop. Dis. 2013, 7, e2484. [Google Scholar] [CrossRef] [PubMed]
  103. Bennett, S.N.; Gu, S.H.; Kang, H.J.; Arai, S.; Yanagihara, R. Reconstructing the evolutionary origins and phylogeography of hantaviruses. Trends Microbiol. 2014, 22, 473–482. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  104. Guterres, A.; de Oliveira, R.C.; Fernandes, J.; de Lemos, E.R.S. Is the evolution of Hantavirus driven by its host? Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis. 2015, 35, 142–143. [Google Scholar] [CrossRef]
  105. Holmes, E.C.; Zhang, Y.-Z. The evolution and emergence of hantaviruses. Curr. Opin. Virol. 2015, 10, 27–33. [Google Scholar] [CrossRef]
  106. Hughes, A.L.; Friedman, R. Evolutionary diversification of protein-coding genes of hantaviruses. Mol. Biol. Evol. 2000, 17, 1558–1568. [Google Scholar] [CrossRef]
  107. Khaiboullina, S.F.; Morzunov, S.P.; St. Jeor, S.C. Hantaviruses: Molecular biology, evolution and pathogenesis. Curr. Mol. Med. 2005, 5, 773–790. [Google Scholar] [CrossRef] [PubMed]
  108. Plyusnin, A.; Morzunov, S.P. Virus evolution and genetic diversity of hantaviruses and their rodent hosts. Curr. Top Microbiol. Immunol. 2001, 256, 47–75. [Google Scholar] [CrossRef]
  109. Plyusnin, A.; Sironen, T. Evolution of hantaviruses: Co-speciation with reservoir hosts for more than 100 MYR. Virus Res. 2014, 187, 22–26. [Google Scholar] [CrossRef]
  110. Ramsden, C.; Holmes, E.C.; Charleston, M.A. Hantavirus evolution in relation to its rodent and insectivore hosts: No evidence for codivergence. Mol. Biol. Evol. 2009, 26, 143–153. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  111. Souza, W.M.; Bello, G.; Amarilla, A.A.; Alfonso, H.L.; Aquino, V.H.; Figueiredo, L.T.M. Phylogeography and evolutionary history of rodent-borne hantaviruses. Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis. 2014, 21, 198–204. [Google Scholar] [CrossRef]
  112. Yanagihara, R. Reconstructing the evolutionary history of hantaviruses. Бюлл ВСНЦ СО РАМН 2012, 5, 155–162. [Google Scholar]
  113. Zhang, Y.-Z.; Holmes, E.C. What is the time-scale of hantavirus evolution? Infect. Genet. Evol. J. Mol. Epidemiol. Evol. Genet. Infect. Dis. 2014, 25, 144–145. [Google Scholar] [CrossRef] [PubMed]
  114. Marklewitz, M.; Zirkel, F.; Kurth, A.; Drosten, C.; Junglen, S. Evolutionary and phenotypic analysis of live virus isolates suggests arthropod origin of a pathogenic RNA virus family. Proc. Natl. Acad. Sci. USA 2015, 112, 7536–7541. [Google Scholar] [CrossRef] [Green Version]
  115. Käfer, S.; Paraskevopoulou, S.; Zirkel, F.; Wieseke, N.; Donath, A.; Petersen, M.; Jones, T.C.; Liu, S.; Zhou, X.; Middendorf, M.; et al. Re-assessing the diversity of negative strand RNA viruses in insects. PLoS Pathog. 2019, 15, e1008224. [Google Scholar] [CrossRef] [Green Version]
  116. Olendraite, I.; Brown, K.; Firth, A.E. Identification of RNA virus-derived RdRp sequences in publicly available transcriptomic datasets. bioRxiv 2022. [Google Scholar] [CrossRef]
  117. Slonova, R.A.; Tkachenko, E.A.; Kushnarev, E.L.; Dzagurova, T.K.; Astakova, T.I. Hantavirus isolation from birds. Acta Virol. 1992, 36, 493. [Google Scholar]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Kuhn, J.H.; Schmaljohn, C.S. A Brief History of Bunyaviral Family Hantaviridae. Diseases 2023, 11, 38.

AMA Style

Kuhn JH, Schmaljohn CS. A Brief History of Bunyaviral Family Hantaviridae. Diseases. 2023; 11(1):38.

Chicago/Turabian Style

Kuhn, Jens H., and Connie S. Schmaljohn. 2023. "A Brief History of Bunyaviral Family Hantaviridae" Diseases 11, no. 1: 38.

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop