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Special Issue "West Nile Virus"

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

Deadline for manuscript submissions: closed (30 November 2013)

Special Issue Editors

Guest Editor
Prof. Dr. Michael S. Diamond

Departments of Medicine, Molecular Microbiology, Pathology & Immunology Washington University School of Medicine Co-Director, Midwest Regional Center for Excellence in Biodefense and Emerging Infectious Disease Research 660 S Euclid Avenue St Louis, MO 63110, USA
Website | E-Mail
Guest Editor
Dr. Ted C. Pierson

Senior Investigator, Laboratory of Viral Diseases, NIAID, NIH, 33 North Drive, Building 33, Room 2E19A.2, Bethesda, MD 20892, USA
Website | E-Mail
Fax: +1 301 451 7978

Special Issue Information

Dear Colleagues,

West Nile virus (WNV) is an emerging mosquito-transmitted zoonotic pathogen that continues to spread throughout regions of the New World, Europe, Africa, and parts of the Middle East. Over the last decade, it has caused millions of human infections with outcomes ranging from sub-clinical illness, to a self-limiting febrile syndrome or lethal neuroinvasive disease. WNV poses a significant global public health risk and thus, has triggered intensive research into many areas related to WNV pathogenesis and disease. Among those targeted for exploration and discussion in this Special Edition are the epidemiology and clinical presentation of WNV disease, the virus-vector interface, vector ecology, WNV evolution and adaptation, the protective mammalian host immune response, mechanisms of virus immune evasion, and strategies for developing effective prophylaxis and treatments.

Prof. Dr. Michael S. Diamond
Dr. Ted C. Pierson
Guest Editors

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs).

Keywords

  • flavivirus
  • pathogenesis
  • encephalitis
  • meningitis
  • humoral immunity
  • cellular immunity
  • neutralization
  • vaccine
  • therapeutics
  • mosquito
  • neuron
  • dendritic cells
  • genetics
  • neurotropism
  • neuronal injury

Related Special Issue

Published Papers (12 papers)

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Research

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Open AccessArticle West Nile Virus in the United States — A Historical Perspective
Viruses 2013, 5(12), 3088-3108; doi:10.3390/v5123088
Received: 29 August 2013 / Revised: 23 October 2013 / Accepted: 29 November 2013 / Published: 10 December 2013
Cited by 25 | PDF Full-text (1421 KB) | HTML Full-text | XML Full-text
Abstract
Prior to 1999, West Nile virus (WNV) was a bit player in the screenplay of global vector-borne viral diseases. First discovered in the West Nile District of Uganda in 1937, this Culex sp.-transmitted virus was known for causing small human febrile outbreaks in
[...] Read more.
Prior to 1999, West Nile virus (WNV) was a bit player in the screenplay of global vector-borne viral diseases. First discovered in the West Nile District of Uganda in 1937, this Culex sp.-transmitted virus was known for causing small human febrile outbreaks in Africa and the Middle East. Prior to 1995, the last major human WNV outbreak was in the 1950s in Israel. The epidemiology and ecology of WNV began to change in the mid-1990s when an epidemic of human encephalitis occurred in Romania. The introduction of WNV into Eastern Europe was readily explained by bird migration between Africa and Europe. The movement of WNV from Africa to Europe could not, however, predict its surprising jump across the Atlantic Ocean to New York City and the surrounding areas of the United States (U.S.). This movement of WNV from the Eastern to Western Hemisphere in 1999, and its subsequent dissemination throughout two continents in less than ten years is widely recognized as one of the most significant events in arbovirology during the last two centuries. This paper documents the early events of the introduction into and the spread of WNV in the Western Hemisphere. Full article
(This article belongs to the Special Issue West Nile Virus)

Review

Jump to: Research

Open AccessReview B Cell Response and Mechanisms of Antibody Protection to West Nile Virus
Viruses 2014, 6(3), 1015-1036; doi:10.3390/v6031015
Received: 17 December 2013 / Revised: 7 February 2014 / Accepted: 8 February 2014 / Published: 3 March 2014
Cited by 2 | PDF Full-text (1370 KB) | HTML Full-text | XML Full-text
Abstract
West Nile virus (WNV) has become the principal cause of viral encephalitis in North America since its introduction in New York in 1999. This emerging virus is transmitted to humans via the bite of an infected mosquito. While there have been several candidates
[...] Read more.
West Nile virus (WNV) has become the principal cause of viral encephalitis in North America since its introduction in New York in 1999. This emerging virus is transmitted to humans via the bite of an infected mosquito. While there have been several candidates in clinical trials, there are no approved vaccines or WNV-specific therapies for the treatment of WNV disease in humans. From studies with small animal models and convalescent human patients, a great deal has been learned concerning the immune response to infection with WNV. Here, we provide an overview of a subset of that information regarding the humoral and antibody response generated during WNV infection. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview Clinical Manifestations and Outcomes of West Nile Virus Infection
Viruses 2014, 6(2), 606-623; doi:10.3390/v6020606
Received: 30 October 2013 / Revised: 20 January 2014 / Accepted: 21 January 2014 / Published: 6 February 2014
Cited by 20 | PDF Full-text (1369 KB) | HTML Full-text | XML Full-text
Abstract
Since the emergence of West Nile virus (WNV) in North America in 1999, understanding of the clinical features, spectrum of illness and eventual functional outcomes of human illness has increased tremendously. Most human infections with WNV remain clinically silent. Among those persons developing
[...] Read more.
Since the emergence of West Nile virus (WNV) in North America in 1999, understanding of the clinical features, spectrum of illness and eventual functional outcomes of human illness has increased tremendously. Most human infections with WNV remain clinically silent. Among those persons developing symptomatic illness, most develop a self-limited febrile illness. More severe illness with WNV (West Nile neuroinvasive disease, WNND) is manifested as meningitis, encephalitis or an acute anterior (polio) myelitis. These manifestations are generally more prevalent in older persons or those with immunosuppression. In the future, a more thorough understanding of the long-term physical, cognitive and functional outcomes of persons recovering from WNV illness will be important in understanding the overall illness burden. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview Noncoding Subgenomic Flavivirus RNA: Multiple Functions in West Nile Virus Pathogenesis and Modulation of Host Responses
Viruses 2014, 6(2), 404-427; doi:10.3390/v6020404
Received: 19 September 2013 / Revised: 13 January 2014 / Accepted: 15 January 2014 / Published: 27 January 2014
Cited by 33 | PDF Full-text (1139 KB) | HTML Full-text | XML Full-text
Abstract
Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested
[...] Read more.
Flaviviruses are a large group of positive strand RNA viruses transmitted by arthropods that include many human pathogens such as West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus, dengue virus, and tick-borne encephalitis virus. All members in this genus tested so far are shown to produce a unique subgenomic flavivirus RNA (sfRNA) derived from the 3' untranslated region (UTR). sfRNA is a product of incomplete degradation of genomic RNA by the cell 5'–3' exoribonuclease XRN1 which stalls at highly ordered secondary RNA structures at the beginning of the 3'UTR. Generation of sfRNA results in inhibition of XRN1 activity leading to an increase in stability of many cellular mRNAs. Mutant WNV deficient in sfRNA generation was highly attenuated displaying a marked decrease in cytopathicity in cells and pathogenicity in mice. sfRNA has also been shown to inhibit the antiviral activity of IFN-α/β by yet unknown mechanism and of the RNAi pathway by likely serving as a decoy substrate for Dicer. Thus, sfRNA is involved in modulating multiple cellular pathways to facilitate viral pathogenicity; however the overlying mechanism linking all these multiple functions of sfRNA remains to be elucidated. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview Flavivirus Entry Receptors: An Update
Viruses 2014, 6(1), 69-88; doi:10.3390/v6010069
Received: 8 October 2013 / Revised: 12 December 2013 / Accepted: 12 December 2013 / Published: 30 December 2013
Cited by 38 | PDF Full-text (1176 KB) | HTML Full-text | XML Full-text
Abstract
Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell
[...] Read more.
Flaviviruses enter host cells by endocytosis initiated when the virus particles interact with cell surface receptors. The current model suggests that flaviviruses use at least two different sets of molecules for infectious entry: attachment factors that concentrate and/or recruit viruses on the cell surface and primary receptor(s) that bind to virions and direct them to the endocytic pathway. Here, we present the currently available knowledge regarding the flavivirus receptors described so far with specific attention to C-type lectin receptors and the phosphatidylserine receptors, T-cell immunoglobulin and mucin domain (TIM) and TYRO3, AXL and MER (TAM). Their role in flavivirus attachment and entry as well as their implication in the virus biology will be discussed in depth. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview Replication Cycle and Molecular Biology of the West Nile Virus
Viruses 2014, 6(1), 13-53; doi:10.3390/v6010013
Received: 21 October 2013 / Revised: 12 December 2013 / Accepted: 12 December 2013 / Published: 27 December 2013
Cited by 25 | PDF Full-text (2769 KB) | HTML Full-text | XML Full-text
Abstract
West Nile virus (WNV) is a member of the genus Flavivirus in the family Flaviviridae. Flaviviruses replicate in the cytoplasm of infected cells and modify the host cell environment. Although much has been learned about virion structure and virion-endosomal membrane fusion, the cell
[...] Read more.
West Nile virus (WNV) is a member of the genus Flavivirus in the family Flaviviridae. Flaviviruses replicate in the cytoplasm of infected cells and modify the host cell environment. Although much has been learned about virion structure and virion-endosomal membrane fusion, the cell receptor(s) used have not been definitively identified and little is known about the early stages of the virus replication cycle. Members of the genus Flavivirus differ from members of the two other genera of the family by the lack of a genomic internal ribosomal entry sequence and the creation of invaginations in the ER membrane rather than double-membrane vesicles that are used as the sites of exponential genome synthesis. The WNV genome 3' and 5' sequences that form the long distance RNA-RNA interaction required for minus strand initiation have been identified and contact sites on the 5' RNA stem loop for NS5 have been mapped. Structures obtained for many of the viral proteins have provided information relevant to their functions. Viral nonstructural protein interactions are complex and some may occur only in infected cells. Although interactions between many cellular proteins and virus components have been identified, the functions of most of these interactions have not been delineated. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview The Role of Innate Immunity in Conditioning Mosquito Susceptibility to West Nile Virus
Viruses 2013, 5(12), 3142-3170; doi:10.3390/v5123142
Received: 29 August 2013 / Revised: 13 November 2013 / Accepted: 9 December 2013 / Published: 13 December 2013
Cited by 7 | PDF Full-text (852 KB) | HTML Full-text | XML Full-text
Abstract
Arthropod-borne viruses (arboviruses) represent an emerging threat to human and livestock health globally. In particular, those transmitted by mosquitoes present the greatest challenges to disease control efforts. An understanding of the molecular basis for mosquito innate immunity to arbovirus infection is therefore critical
[...] Read more.
Arthropod-borne viruses (arboviruses) represent an emerging threat to human and livestock health globally. In particular, those transmitted by mosquitoes present the greatest challenges to disease control efforts. An understanding of the molecular basis for mosquito innate immunity to arbovirus infection is therefore critical to investigations regarding arbovirus evolution, virus-vector ecology, and mosquito vector competence. In this review, we discuss the current state of understanding regarding mosquito innate immunity to West Nile virus. We draw from the literature with respect to other virus-vector pairings to attempt to draw inferences to gaps in our knowledge about West Nile virus and relevant vectors. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview West Nile Virus Drug Discovery
Viruses 2013, 5(12), 2977-3006; doi:10.3390/v5122977
Received: 3 October 2013 / Revised: 25 November 2013 / Accepted: 25 November 2013 / Published: 3 December 2013
Cited by 11 | PDF Full-text (932 KB) | HTML Full-text | XML Full-text
Abstract
The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug
[...] Read more.
The outbreak of West Nile virus (WNV) in 1999 in the USA, and its continued spread throughout the Americas, parts of Europe, the Middle East and Africa, underscored the need for WNV antiviral development. Here, we review the current status of WNV drug discovery. A number of approaches have been used to search for inhibitors of WNV, including viral infection-based screening, enzyme-based screening, structure-based virtual screening, structure-based rationale design, and antibody-based therapy. These efforts have yielded inhibitors of viral or cellular factors that are critical for viral replication. For small molecule inhibitors, no promising preclinical candidate has been developed; most of the inhibitors could not even be advanced to the stage of hit-to-lead optimization due to their poor drug-like properties. However, several inhibitors developed for related members of the family Flaviviridae, such as dengue virus and hepatitis C virus, exhibited cross-inhibition of WNV, suggesting the possibility to re-purpose these antivirals for WNV treatment. Most promisingly, therapeutic antibodies have shown excellent efficacy in mouse model; one of such antibodies has been advanced into clinical trial. The knowledge accumulated during the past fifteen years has provided better rationale for the ongoing WNV and other flavivirus antiviral development. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview The Innate Immune Playbook for Restricting West Nile Virus Infection
Viruses 2013, 5(11), 2643-2658; doi:10.3390/v5112643
Received: 8 September 2013 / Revised: 19 October 2013 / Accepted: 22 October 2013 / Published: 30 October 2013
Cited by 12 | PDF Full-text (513 KB) | HTML Full-text | XML Full-text
Abstract
West Nile virus (WNV) is an emerging mosquito-borne flavivirus that causes annual epidemics of encephalitic disease throughout the world. Despite the ongoing risk to public health, no approved vaccines or therapies exist for use in humans to prevent or combat WNV infection. The
[...] Read more.
West Nile virus (WNV) is an emerging mosquito-borne flavivirus that causes annual epidemics of encephalitic disease throughout the world. Despite the ongoing risk to public health, no approved vaccines or therapies exist for use in humans to prevent or combat WNV infection. The innate immune response is critical for controlling WNV replication, limiting virus-induced pathology, and programming protective humoral and cell-mediated immunity to WNV infection. The RIG-I like receptors, Toll-like receptors, and Nod-like receptors detect and respond to WNV by inducing a potent antiviral defense program, characterized by production of type I IFN, IL-1β and expression of antiviral effector genes. Recent research efforts have focused on uncovering the mechanisms of innate immune sensing, antiviral effector genes that inhibit WNV, and countermeasures employed by WNV to antagonize innate immune cellular defenses. In this review, we highlight the major research findings pertaining to innate immune regulation of WNV infection. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview CD8 and CD4 T Cells in West Nile Virus Immunity and Pathogenesis
Viruses 2013, 5(10), 2573-2584; doi:10.3390/v5102573
Received: 2 September 2013 / Revised: 5 October 2013 / Accepted: 14 October 2013 / Published: 22 October 2013
Cited by 8 | PDF Full-text (257 KB) | HTML Full-text | XML Full-text
Abstract
CD4 and CD8 T lymphocytes are adaptive immune cells that play a key role in the immune response to pathogens. They have been extensively studied in a variety of model systems and the mechanisms by which they function are well described. However, the
[...] Read more.
CD4 and CD8 T lymphocytes are adaptive immune cells that play a key role in the immune response to pathogens. They have been extensively studied in a variety of model systems and the mechanisms by which they function are well described. However, the responses by these cell types vary widely from pathogen to pathogen. In this review, we will discuss the role of CD8 and CD4 T cells in the immune response to West Nile virus infection. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview Role of Natural Killer and Gamma-Delta T cells in West Nile Virus Infection
Viruses 2013, 5(9), 2298-2310; doi:10.3390/v5092298
Received: 25 July 2013 / Revised: 30 August 2013 / Accepted: 16 September 2013 / Published: 20 September 2013
Cited by 10 | PDF Full-text (428 KB) | HTML Full-text | XML Full-text
Abstract
Natural Killer (NK) cells and Gamma-delta T cells are both innate lymphocytes that respond rapidly and non-specifically to viral infection and other pathogens. They are also known to form a unique link between innate and adaptive immunity. Although they have similar immune features
[...] Read more.
Natural Killer (NK) cells and Gamma-delta T cells are both innate lymphocytes that respond rapidly and non-specifically to viral infection and other pathogens. They are also known to form a unique link between innate and adaptive immunity. Although they have similar immune features and effector functions, accumulating evidence in mice and humans suggest these two cell types have distinct roles in the control of infection by West Nile virus (WNV), a re-emerging pathogen that has caused fatal encephalitis in North America over the past decade. This review will discuss recent studies on these two cell types in protective immunity and viral pathogenesis during WNV infection. Full article
(This article belongs to the Special Issue West Nile Virus)
Open AccessReview Ecology of West Nile Virus in North America
Viruses 2013, 5(9), 2079-2105; doi:10.3390/v5092079
Received: 5 August 2013 / Accepted: 25 August 2013 / Published: 4 September 2013
Cited by 30 | PDF Full-text (1235 KB) | HTML Full-text | XML Full-text
Abstract
The introduction, dispersal and establishment of West Nile virus in North America were reviewed, focusing on factors that may have enhanced receptivity and enabled the invasion process. The overwintering persistence of this tropical virus within temperate latitudes was unexpected, but was key in
[...] Read more.
The introduction, dispersal and establishment of West Nile virus in North America were reviewed, focusing on factors that may have enhanced receptivity and enabled the invasion process. The overwintering persistence of this tropical virus within temperate latitudes was unexpected, but was key in the transition from invasion to endemic establishment. The cascade of temporal events allowing sporadic amplification to outbreak levels was discussed within a future perspective. Full article
(This article belongs to the Special Issue West Nile Virus)

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