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Viruses
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Animal Herpesvirus
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Animal Herpesvirus

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 11136

Special Issue Editor

Prof. Dr. Shafiqul Chowdhury

E-Mail Website
Guest Editor
Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
Interests: veterinary virology; graduate level advanced virology; bovine herpesvirus type 1 (BHV-1); equine herpesvirus type 1 (EHV-1) pathogenesis; genetically engineered vaccines; vaccine vector
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Herpesviruses are ubiquitous pathogens and are excellent managers of the host immune response. They can successfully survive in the host, as in the case of alphaherpesviruses. Therefore, herpesviruses have a long history of co-evolution with the host species. They might have originated from a common ancestor of mammals and birds, and evolved and learned to adapt to their respective host using various survival strategies over time. However, there seems to be a common theme among the herpesviruses of different host species, for example, initial diversion or counteraction against innate immune responses and later evasion from host adaptive immune responses. Therefore, animal herpesvirus pathogenesis involves a delicate, yet dynamic interplay between the host and the virus. Since herpesviruses are part of a virome and may remain in their respective animal hosts for life, they can also impact susceptibility to other infections and disease-producing agents. For this Special Issue, we invite the submission of original research papers and review articles spanning the entire spectrum of herpesvirus–host interactions in different animal species from both the virus and host perspectives. Articles that present strategies for future vaccine development considering the complexity of host–virus interactions and the complications resulting from dual infections that include herpesvirus-mediated disease complexes in different animal host species are also welcome.

Prof. Dr. Shafiqul Chowdhury
Guest Editor

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Keywords

  • herpesviruses
  • innate immune responses
  • host adaptive immune responses
  • herpesvirus–host
  • interactions
  • susceptibility

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Published Papers (9 papers)

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Research

13 pages, 3471 KiB  
Article
Bovine Transcription Factor POU Class 2 Homeobox 1 (POU2F1/Oct1) Protein Promotes BoHV-1 Replication in MDBK Cells
by Enguang Rong, Inga Dry, Robert G. Dalziel and Wenfang Spring Tan
Viruses 2024, 16(10), 1549; https://doi.org/10.3390/v16101549 - 30 Sep 2024
Viewed by 420
Abstract
Bovine herpesvirus type 1 (BoHV-1) causes severe diseases in bovine species and great economic burden to the cattle industry worldwide. Due to its complex life cycle, many host factors that affect BoHV-1 replication remain to be explored. To understand the possible roles that [...] Read more.
Bovine herpesvirus type 1 (BoHV-1) causes severe diseases in bovine species and great economic burden to the cattle industry worldwide. Due to its complex life cycle, many host factors that affect BoHV-1 replication remain to be explored. To understand the possible roles that the Oct1 cellular protein could play in this process, we first created Oct1-deficient MDBK cells using CRISPR/Cas9-mediated genome editing. Upon infection, the absence of Oct1 in MDBK cells significantly impacted BoHV-1 replication, a phenotype rescued by over-expressing the wild-type Oct1 protein in the deficient cells. We further found that the expression of all three classes of temporal genes, including essential and non-essential viral genes, were significantly reduced in Oct1 knockout MDBK cells, following both high and low multiplicity of infection. In summary, our findings confirm that the bovine Oct1 protein acts as a pro-viral factor for BoHV-1 replication by promoting its viral gene transcription in MDBK cells. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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19 pages, 2675 KiB  
Article
Characterization of Nasal Mucosal T Cells in Horses and Their Response to Equine Herpesvirus Type 1
by Camille M. Holmes and Bettina Wagner
Viruses 2024, 16(10), 1514; https://doi.org/10.3390/v16101514 - 25 Sep 2024
Viewed by 576
Abstract
Equine herpesvirus type 1 (EHV-1) enters through the upper respiratory tract (URT). Mucosal immunity at the URT is crucial in limiting viral infection and morbidity. Here, intranasal immune cells were collected from horses (n = 15) during an experimental EHV-1 infection. CD4 [...] Read more.
Equine herpesvirus type 1 (EHV-1) enters through the upper respiratory tract (URT). Mucosal immunity at the URT is crucial in limiting viral infection and morbidity. Here, intranasal immune cells were collected from horses (n = 15) during an experimental EHV-1 infection. CD4+ and CD8+ T cells were the major intranasal cell populations before infection and increased significantly by day six and fourteen post-infection, respectively. Nasal mucosal T cells were further characterized in healthy horses. Compared to peripheral blood mononuclear cells (PBMC), mucosal CD8+ T-cell percentages were elevated, while CD4+ T-cell percentages were similar. A small population of CD4+CD8+ T cells was also recovered from mucosal samples. Within the URT tissue, CD4+ cells predominantly accumulated in the epithelial layer, while most CD8+ cells resided deeper in the mucosa or the submucosa below the basement membrane. In vitro stimulation of mucosal cells from healthy horses with (n = 5) or without (n = 5) peripheral T-cell immunity against EHV-1 induced IFN-γ production in nasal T cells upon polyclonal stimulation. However, after EHV-1 re-stimulation, mucosal T cells failed to respond with IFN-γ. This work provided the first characterization of mucosal T-cell phenotypes and functions in the URT of healthy horses and during EHV-1 infection. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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Graphical abstract

16 pages, 5902 KiB  
Article
Novel Gammaherpesvirus Infections in Narrow-Ridged Finless Porpoise (Neophocaena asiaeorientalis) and False Killer Whales (Pseudorca crassidens) in the Republic of Korea
by Sung Bin Lee, Kyung Lee Lee, Sang Wha Kim, Won Joon Jung, Da Sol Park, Seyoung Lee, Sib Sankar Giri, Sang Guen Kim, Su Jin Jo, Jae Hong Park, Mae Hyun Hwang, Eun Jae Park, Jong-pil Seo, Byung Yeop Kim and Se Chang Park
Viruses 2024, 16(8), 1234; https://doi.org/10.3390/v16081234 - 31 Jul 2024
Viewed by 870
Abstract
A female narrow-ridged finless porpoise (Neophocaena asiaeorientalis) stranded on a beach on Jeju Island showed epithelial proliferative skin lesions on its body. Two false killer whales (Pseudorca crassidens), caught using nets near Gangneung and Samcheok, respectively, had multiple plaques [...] Read more.
A female narrow-ridged finless porpoise (Neophocaena asiaeorientalis) stranded on a beach on Jeju Island showed epithelial proliferative skin lesions on its body. Two false killer whales (Pseudorca crassidens), caught using nets near Gangneung and Samcheok, respectively, had multiple plaques on their penile epidermis. Histological examination of the epidermis revealed that all the lesions had common features, including accentuated rete pegs, ballooning changes, and eosinophilic intranuclear inclusion (INI) bodies. Based on the histopathological results, herpesvirus infection was suspected, and thus further analysis was conducted using herpesvirus-specific primers. Based on nested polymerase chain reaction (PCR) tests using the herpesvirus-detectable primers, the PCR products demonstrated two fragments: a 222-base-pair (bp) sequence of the DNA polymerase gene, SNUABM_CeHV01, showing 96.4% identity with a bottlenose dolphin herpesvirus from the Jeju narrow-ridged finless porpoise; and a 222 bp sequence of the DNA polymerase gene, SNUABM_CeHV02, showing 95.95% identity with the same bottlenose dolphin herpesvirus from the Gangneung and Samcheok false killer whales. The significance of this study lies in its ability to demonstrate the existence of novel cetacean herpesviruses in South Korean seawater, representing an important step forward in studying potentially harmful pathogens that affect endangered whale and dolphin populations. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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15 pages, 1716 KiB  
Article
Aspergillus Fumigatus Spore Proteases Alter the Respiratory Mucosa Architecture and Facilitate Equine Herpesvirus 1 Infection
by Joren Portaels, Eline Van Crombrugge, Wim Van Den Broeck, Katrien Lagrou, Kathlyn Laval and Hans Nauwynck
Viruses 2024, 16(8), 1208; https://doi.org/10.3390/v16081208 - 27 Jul 2024
Viewed by 751
Abstract
Numerous Aspergillus fumigatus (Af) airborne spores are inhaled daily by humans and animals due to their ubiquitous presence. The interaction between the spores and the respiratory epithelium, as well as its impact on the epithelial barrier function, remains largely unknown. The epithelial barrier [...] Read more.
Numerous Aspergillus fumigatus (Af) airborne spores are inhaled daily by humans and animals due to their ubiquitous presence. The interaction between the spores and the respiratory epithelium, as well as its impact on the epithelial barrier function, remains largely unknown. The epithelial barrier protects the respiratory epithelium against viral infections. However, it can be compromised by environmental contaminants such as pollen, thereby increasing susceptibility to respiratory viral infections, including alphaherpesvirus equine herpesvirus type 1 (EHV-1). To determine whether Af spores disrupt the epithelial integrity and enhance susceptibility to viral infections, equine respiratory mucosal ex vivo explants were pretreated with Af spore diffusate, followed by EHV-1 inoculation. Spore proteases were characterized by zymography and identified using mass spectrometry-based proteomics. Proteases of the serine protease, metalloprotease, and aspartic protease groups were identified. Morphological analysis of hematoxylin-eosin (HE)-stained sections of the explants revealed that Af spores induced the desquamation of epithelial cells and a significant increase in intercellular space at high and low concentrations, respectively. The increase in intercellular space in the epithelium caused by Af spore proteases correlated with an increase in EHV-1 infection. Together, our findings demonstrate that Af spore proteases disrupt epithelial integrity, potentially leading to increased viral infection of the respiratory epithelium. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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12 pages, 1340 KiB  
Article
Bovine Alphaherpesvirus 1, Bovine Alphaherpesvirus 5 and Bubaline Alphaherpesvirus 1 in Palatine Tonsils from Water Buffaloes in Northern Brazil and Possible Links with the Origin of Bovine Alphaherpesvirus Type 5
by Bruna Paredes-Galarza, Martha T. Oliveira, Francine B. Timm, Nicole V. Stone, Lina Violet-Lozano, Richard S. Salvato, Nícolas D. Müller, Bruno A. Prandi, Raíssa Gasparetto, Michelen Gonçalves, María A. S. Teixeira, Márcio A. O. Moura, Gabriela Riet-Correa, Valíria D. Cerqueira, Pedro S. Bezerra, Jr., Fabrício S. Campos, Ana C. Franco and Paulo M. Roehe
Viruses 2024, 16(7), 1024; https://doi.org/10.3390/v16071024 - 26 Jun 2024
Viewed by 1214
Abstract
Herpesviruses are significant pathogens of ruminants. In water buffaloes (Bubalus bubalis), however, herpesviruses have not been thoroughly studied. Although bubaline alphaherpesvirus 1 (BuAHV1) and bovine alphaherpesvirus 1 (BoAHV1) have already been recovered from water buffaloes, to date, no reports on the [...] Read more.
Herpesviruses are significant pathogens of ruminants. In water buffaloes (Bubalus bubalis), however, herpesviruses have not been thoroughly studied. Although bubaline alphaherpesvirus 1 (BuAHV1) and bovine alphaherpesvirus 1 (BoAHV1) have already been recovered from water buffaloes, to date, no reports on the occurrence of bovine alphaherpesvirus 5 (BoAHV5) in these animals have been published. Therefore, the aim of this study was to search for BuAHV1, BoAHV1, and BoAHV5 in palatine tonsils of apparently healthy water buffaloes from the Pará state, Northern Brazil. Tissue samples of tonsils (n = 293) were screened by a nested PCR (nPCR) targeting a region of UL44 (gC coding gene), followed by sequencing, to detect and differentiate between the viral types. Viral genome segments were detected in 18 out of 293 (6.1%) of the palatine tonsil samples. Two animals carried genomes of BoAHV1 only, eleven animals carried BoAHV5 genomes only, and four animals carried BuAHV1 only. Another animal had both BoAHV1 and BoAHV5 genomes in its tonsils. No infectious virus could be recovered from any of the samples. The BuAHV1 sequences identified here were more closely related to BuAHV1 genomes identified in India. Phylogenetic analyses suggested a closer relationship between the recovered BoAHV5 and BuAHV1 genomes. Therefore, evidence is provided here to confirm that not only BoAHV1 and BuAHV1, but also BoAHV5, can infect water buffaloes. This report highlights (i) the first detection of BoAHV5 in water buffaloes and (ii) the occurrence of coinfections with BoAHV1 and BoAHV5 in that species. Such findings and the similarity of BoAHV5 to Indian herpesvirus genomes suggest that the origin of type 5 may be linked to recombinations between bovine and bubaline herpesviruses within bubalines, since the scenario for generation of recombinants in buffaloes is potentially present. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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20 pages, 3278 KiB  
Article
Modulation of Equid Herpesvirus-1 Replication Dynamics In Vitro Using CRISPR/Cas9-Assisted Genome Editing
by Rabab T. Hassanien, Côme J. Thieulent, Mariano Carossino, Ganwu Li and Udeni B. R. Balasuriya
Viruses 2024, 16(3), 409; https://doi.org/10.3390/v16030409 - 6 Mar 2024
Cited by 2 | Viewed by 1368
Abstract
(1) Background: equid alphaherpesvirus-1 (EHV-1) is a highly contagious viral pathogen prevalent in most horse populations worldwide. Genome-editing technologies such as CRISPR/Cas9 have become powerful tools for precise RNA-guided genome modifications; (2) Methods: we designed single guide RNAs (sgRNA) to target three essential [...] Read more.
(1) Background: equid alphaherpesvirus-1 (EHV-1) is a highly contagious viral pathogen prevalent in most horse populations worldwide. Genome-editing technologies such as CRISPR/Cas9 have become powerful tools for precise RNA-guided genome modifications; (2) Methods: we designed single guide RNAs (sgRNA) to target three essential (ORF30, ORF31, and ORF7) and one non-essential (ORF74) EHV-1 genes and determine their effect on viral replication dynamics in vitro; (3) Results: we demonstrated that sgRNAs targeting essential lytic genes reduced EHV-1 replication, whereas those targeting ORF74 had a negligible effect. The sgRNAs targeting ORF30 showed the strongest effect on the suppression of EHV-1 replication, with a reduction in viral genomic copy numbers and infectious progeny virus output. Next-generation sequencing identified variants with deletions in the specific cleavage site of selective sgRNAs. Moreover, we evaluated the combination between different sgRNAs and found that the dual combination of sgRNAs targeting ORF30 and ORF7 significantly suppressed viral replication to lower levels compared to the use of a single sgRNA, suggesting a synergic effect; (4) Conclusion: data demonstrate that sgRNA-guided CRISPR/Cas9 can be used to inhibit EHV-1 replication in vitro, indicating that this programmable technique can be used to develop a novel, safe, and efficacious therapeutic and prophylactic approach against EHV-1. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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22 pages, 4171 KiB  
Article
Validation of Candidate Host Cell Entry Factors for Bovine Herpes Virus Type-1 Based on a Genome-Wide CRISPR Knockout Screen
by Wenfang Spring Tan, Enguang Rong, Inga Dry, Simon Lillico, Andy Law, Paul Digard, Bruce Whitelaw and Robert G. Dalziel
Viruses 2024, 16(2), 297; https://doi.org/10.3390/v16020297 - 15 Feb 2024
Viewed by 1983
Abstract
To identify host factors that affect Bovine Herpes Virus Type 1 (BoHV-1) infection we previously applied a genome wide CRISPR knockout screen targeting all bovine protein coding genes. By doing so we compiled a list of both pro-viral and anti-viral proteins involved in [...] Read more.
To identify host factors that affect Bovine Herpes Virus Type 1 (BoHV-1) infection we previously applied a genome wide CRISPR knockout screen targeting all bovine protein coding genes. By doing so we compiled a list of both pro-viral and anti-viral proteins involved in BoHV-1 replication. Here we provide further analysis of those that are potentially involved in viral entry into the host cell. We first generated single cell knockout clones deficient in some of the candidate genes for validation. We provide evidence that Polio Virus Receptor-related protein (PVRL2) serves as a receptor for BoHV-1, mediating more efficient entry than the previously identified Polio Virus Receptor (PVR). By knocking out two enzymes that catalyze HSPG chain elongation, HST2ST1 and GLCE, we further demonstrate the significance of HSPG in BoHV-1 entry. Another intriguing cluster of candidate genes, COG1, COG2 and COG4-7 encode six subunits of the Conserved Oligomeric Golgi (COG) complex. MDBK cells lacking COG6 produced fewer but bigger plaques compared to control cells, suggesting more efficient release of newly produced virions from these COG6 knockout cells, due to impaired HSPG biosynthesis. We further observed that viruses produced by the COG6 knockout cells consist of protein(s) with reduced N-glycosylation, potentially explaining their lower infectivity. To facilitate candidate validation, we also detailed a one-step multiplex CRISPR interference (CRISPRi) system, an orthogonal method to KO that enables quick and simultaneous deployment of three CRISPRs for efficient gene inactivation. Using CRISPR3i, we verified eight candidates that have been implicated in the synthesis of surface heparan sulfate proteoglycans (HSPGs). In summary, our experiments confirmed the two receptors PVR and PVRL2 for BoHV-1 entry into the host cell and other factors that affect this process, likely through the direct or indirect roles they play during HSPG synthesis and glycosylation of viral proteins. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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18 pages, 3792 KiB  
Article
Low gH/gL (Sub)Species-Specific Antibody Levels Indicate Elephants at Risk of Fatal Elephant Endotheliotropic Herpesvirus Hemorrhagic Disease
by Tabitha E. Hoornweg, Willem Schaftenaar, Victor P. M. G. Rutten and Cornelis A. M. de Haan
Viruses 2024, 16(2), 268; https://doi.org/10.3390/v16020268 - 8 Feb 2024
Cited by 1 | Viewed by 1798
Abstract
Elephant endotheliotropic herpesviruses (EEHVs), of which eleven (sub)species are currently distinguished, infect either Asian (Elephas maximus) or African elephants (Loxodonta species). While all adult elephants are latently infected with at least one EEHV (sub)species, young elephants, specifically those with low [...] Read more.
Elephant endotheliotropic herpesviruses (EEHVs), of which eleven (sub)species are currently distinguished, infect either Asian (Elephas maximus) or African elephants (Loxodonta species). While all adult elephants are latently infected with at least one EEHV (sub)species, young elephants, specifically those with low to non-detectable EEHV-specific antibody levels, may develop fatal hemorrhagic disease (EEHV-HD) upon infection. However, animals with high antibody levels against EEHV(1A) gB, an immunodominant antigen recognized by antibodies elicited against multiple (sub)species, may also occasionally succumb to EEHV-HD. To better define which animals are at risk of EEHV-HD, gB and gH/gL ELISAs were developed for each of the Asian elephant EEHV subspecies and assessed using 396 sera from 164 Asian elephants from European zoos. Antibody levels measured against gB of different (sub)species correlated strongly with one another, suggesting high cross-reactivity. Antibody levels against gH/gL of different subspecies were far less correlated and allowed differentiation between these (sub)species. Importantly, while high gB-specific antibody levels were detected in the sera of several EEHV-HD fatalities, all fatalities (n = 23) had low antibody levels against gH/gL of the subspecies causing disease. Overall, our data indicate that (sub)species-specific gH/gL ELISAs can be used to identify animals at risk of EEHV-HD when infected with a particular EEHV (sub)species. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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15 pages, 17100 KiB  
Article
Saikosaponin B2, Punicalin, and Punicalagin in Vitro Block Cellular Entry of Feline Herpesvirus-1
by Bin Liu, Xiao-Qian Jiao, Xu-Feng Dong, Pei Guo, Shu-Bai Wang and Zhi-Hua Qin
Viruses 2024, 16(2), 231; https://doi.org/10.3390/v16020231 - 1 Feb 2024
Viewed by 1194
Abstract
In the realm of clinical practice, nucleoside analogs are the prevailing antiviral drugs employed to combat feline herpesvirus-1 (FHV-1) infections. However, these drugs, initially formulated for herpes simplex virus (HSV) infections, operate through a singular mechanism and are susceptible to the emergence of [...] Read more.
In the realm of clinical practice, nucleoside analogs are the prevailing antiviral drugs employed to combat feline herpesvirus-1 (FHV-1) infections. However, these drugs, initially formulated for herpes simplex virus (HSV) infections, operate through a singular mechanism and are susceptible to the emergence of drug resistance. These challenges underscore the imperative to innovate and develop alternative antiviral medications featuring unique mechanisms of action, such as viral entry inhibitors. This research endeavors to address this pressing need. Utilizing Bio-layer interferometry (BLI), we meticulously screened drugs to identify natural compounds exhibiting high binding affinity for the herpesvirus functional protein envelope glycoprotein B (gB). The selected drugs underwent a rigorous assessment to gauge their antiviral activity against feline herpesvirus-1 (FHV-1) and to elucidate their mode of action. Our findings unequivocally demonstrated that Saikosaponin B2, Punicalin, and Punicalagin displayed robust antiviral efficacy against FHV-1 at concentrations devoid of cytotoxicity. Specifically, these compounds, Saikosaponin B2, Punicalin, and Punicalagin, are effective in exerting their antiviral effects in the early stages of viral infection without compromising the integrity of the viral particle. Considering the potency and efficacy exhibited by Saikosaponin B2, Punicalin, and Punicalagin in impeding the early entry of FHV-1, it is foreseeable that their chemical structures will be further explored and developed as promising antiviral agents against FHV-1 infection. Full article
(This article belongs to the Special Issue Animal Herpesvirus)
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