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Viruses
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Advances in Flavivirus Research
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Advances in Flavivirus Research

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

Deadline for manuscript submissions: closed (1 December 2016) | Viewed by 120278

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Michael R. Holbrook

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Guest Editor
Battelle Memorial Institute/NIAID Integrated Research Facility Ft. Detrick, MD 21702, USA
Interests: yellow fever virus; tick-borne encephalitis virus; Nipah virus; cell mediated immunity; virus-host cell interactions

Special Issue Information

Dear Colleagues,

Members of the genus Flavivirus cause diseases ranging from mild, acute febrile disease to severe neurological or hemorrhagic diseases.  With the current outbreaks of Zika and yellow fever virus infections, the interest in these arthropod-borne viruses is exceptionally high.  In addition, the progression of dengue vaccines into advanced clinical trials and licensure in some countries marks a historic achievement for the development of vaccines against this disease.  While the development of dengue vaccines adds to the array of vaccines available to prevent disease following flavivirus infection, the lack of therapeutics for the treatment of flavivirus infections is a glaring limitation in our ability to manage diseases caused by these viruses.  The lack of effective animal models for many flavivirus infections also severely hampers research toward development of medical countermeasures.

In this special issue of Viruses, we aim to assemble a collection of research papers and reviews that highlight critical advancements in our understanding of flavivirus pathogenesis and countermeasure development. Of particular interest are the development of novel animal models, the immune responses to flavivirus infection, virus-host cell interactions to include intracellular signaling and entry/egress processes, vector-host interactions, novel discoveries in flavivirus pathogenesis, vaccine development and advances in medical countermeasure development.

Dr. Michael Holbrook
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind 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 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cell-mediated response to flavivirus infection
  • Flavivirus animal models
  • Flavivirus vector interactions
  • Yellow fever virus
  • Zika virus
  • Tick-borne encephalitis virus
  • Japanese encephalitis virus
  • West Nile encephalitis
  • Therapeutics for flavivirus infection
  • Flavivirus vaccines

Published Papers (14 papers)

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Research

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1522 KiB  
Article
Prevalence and Clinical Impact of Human Pegivirus-1 Infection in HIV-1-Infected Individuals in Yunnan, China
by Zhijiang Miao, Li Gao, Yindi Song, Ming Yang, Mi Zhang, Jincheng Lou, Yue Zhao, Xicheng Wang, Yue Feng, Xingqi Dong and Xueshan Xia
Viruses 2017, 9(2), 28; https://0-doi-org.brum.beds.ac.uk/10.3390/v9020028 - 15 Feb 2017
Cited by 26 | Viewed by 5871
Abstract
Human Pegivirus-1 (HPgV-1) may have a beneficial impact on disease progression in human immunodeficiency virus-1 (HIV-1) infection. However, analysis of the genotypic diversity of HPgV-1 and its relevance to the progression of HIV-1 disease remains limited. A total of 1062 HIV-1-infected individuals were [...] Read more.
Human Pegivirus-1 (HPgV-1) may have a beneficial impact on disease progression in human immunodeficiency virus-1 (HIV-1) infection. However, analysis of the genotypic diversity of HPgV-1 and its relevance to the progression of HIV-1 disease remains limited. A total of 1062 HIV-1-infected individuals were recruited in all sixteen prefectures of Yunnan province, China. The reverse transcription nested polymerase chain reaction (RT-nPCR), phylogenetic analyses, and clinical data analyses were used to detect HPgV-1 infection, determine genotype, and analyze HPgV-1 genotype impact on HIV-1 disease progression. The overall positive rate of HPgV-1 RNA was 23.4% (248/1062), and the frequency of HPgV-1 infection in injecting drug users (IDUs) (28.5%, 131/460) was significantly higher than in heterosexuals (19.4%, 117/602). Multiple genotypes were identified in 212 subjects with successful sequencing for the E2 gene, including genotype 7 (55.7%), genotype 3 (34.9%), genotype 4 (4.7%), genotype 2 (3.3%), and an unclassified group (1.4%). Moreover, genotype 7 predominated in IDUs, whereas genotype 3 was the most common in heterosexuals. Our results revealed that HPgV-1 genotype 7 groups exhibited significantly lower HIV-1 viral load and higher CD4+ cell counts. This finding suggests that HPgV-1 genotype 7 may be associated with a better progression of HIV-1 disease. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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1413 KiB  
Article
Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain
by Jian Yang, Huiqiang Yang, Zhushi Li, Wei Wang, Hua Lin, Lina Liu, Qianzhi Ni, Xinyu Liu, Xianwu Zeng, Yonglin Wu and Yuhua Li
Viruses 2017, 9(1), 20; https://0-doi-org.brum.beds.ac.uk/10.3390/v9010020 - 21 Jan 2017
Cited by 35 | Viewed by 5561
Abstract
The attenuated Japanese encephalitis virus (JEV) strain SA14-14-2 has been successfully utilized to prevent JEV infection; however, the attenuation determinants have not been fully elucidated. The envelope (E) protein of the attenuated JEV SA14-14-2 strain differs from that of the virulent parental SA14 [...] Read more.
The attenuated Japanese encephalitis virus (JEV) strain SA14-14-2 has been successfully utilized to prevent JEV infection; however, the attenuation determinants have not been fully elucidated. The envelope (E) protein of the attenuated JEV SA14-14-2 strain differs from that of the virulent parental SA14 strain at eight amino acid positions (E107, E138, E176, E177, E264, E279, E315, and E439). Here, we investigated the SA14-14-2-attenuation determinants by mutating E107, E138, E176, E177, and E279 in SA14-14-2 to their status in the parental virulent strain and tested the replication capacity, neurovirulence, neuroinvasiveness, and mortality associated with the mutated viruses in mice, as compared with those of JEV SA14-14-2 and SA14. Our findings indicated that revertant mutations at the E138 or E107 position significantly increased SA14-14-2 virulence, whereas other revertant mutations exhibited significant increases in neurovirulence only when combined with E138, E107, and other mutations. Revertant mutations at all eight positions in the E protein resulted in the highest degree of SA14-14-2 virulence, although this was still lower than that observed in SA14. These results demonstrated the critical role of the viral E protein in controlling JEV virulence and identified the amino acids at the E107 and E138 positions as the key determinants of SA14-14-2 neurovirulence. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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9150 KiB  
Article
Mx Is Not Responsible for the Antiviral Activity of Interferon-α against Japanese Encephalitis Virus
by Jing Zhou, Shi-Qi Wang, Jian-Chao Wei, Xiao-Min Zhang, Zhi-Can Gao, Ke Liu, Zhi-Yong Ma, Pu-Yan Chen and Bin Zhou
Viruses 2017, 9(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/v9010005 - 10 Jan 2017
Cited by 13 | Viewed by 6233
Abstract
Mx proteins are interferon (IFN)-induced dynamin-like GTPases that are present in all vertebrates and inhibit the replication of myriad viruses. However, the role Mx proteins play in IFN-mediated suppression of Japanese encephalitis virus (JEV) infection is unknown. In this study, we set out [...] Read more.
Mx proteins are interferon (IFN)-induced dynamin-like GTPases that are present in all vertebrates and inhibit the replication of myriad viruses. However, the role Mx proteins play in IFN-mediated suppression of Japanese encephalitis virus (JEV) infection is unknown. In this study, we set out to investigate the effects of Mx1 and Mx2 expression on the interferon-α (IFNα) restriction of JEV replication. To evaluate whether the inhibitory activity of IFNα on JEV is dependent on Mx1 or Mx2, we knocked down Mx1 or Mx2 with siRNA in IFNα-treated PK-15 cells and BHK-21 cells, then challenged them with JEV; the production of progeny virus was assessed by plaque assay, RT-qPCR, and Western blotting. Our results demonstrated that depletion of Mx1 or Mx2 did not affect JEV restriction imposed by IFNα, although these two proteins were knocked down 66% and 79%, respectively. Accordingly, expression of exogenous Mx1 or Mx2 did not change the inhibitory activity of IFNα to JEV. In addition, even though virus-induced membranes were damaged by Brefeldin A (BFA), overexpressing porcine Mx1 or Mx2 did not inhibit JEV proliferation. We found that BFA inhibited JEV replication, not maturation, suggesting that BFA could be developed into a novel antiviral reagent. Collectively, our findings demonstrate that IFNα inhibits JEV infection by Mx-independent pathways. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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1333 KiB  
Article
Equine Immunoglobulin and Equine Neutralizing F(ab′)2 Protect Mice from West Nile Virus Infection
by Jiannan Cui, Yongkun Zhao, Hualei Wang, Boning Qiu, Zengguo Cao, Qian Li, Yanbo Zhang, Feihu Yan, Hongli Jin, Tiecheng Wang, Weiyang Sun, Na Feng, Yuwei Gao, Jing Sun, Yanqun Wang, Stanley Perlman, Jincun Zhao, Songtao Yang and Xianzhu Xia
Viruses 2016, 8(12), 332; https://0-doi-org.brum.beds.ac.uk/10.3390/v8120332 - 18 Dec 2016
Cited by 4 | Viewed by 5213
Abstract
West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to [...] Read more.
West Nile virus (WNV) is prevalent in Africa, Europe, the Middle East, West Asia, and North America, and causes epidemic encephalitis. To date, no effective therapy for WNV infection has been developed; therefore, there is urgent need to find an efficient method to prevent WNV disease. In this study, we prepared and evaluated the protective efficacy of immune serum IgG and pepsin-digested F(ab′)2 fragments from horses immunized with the WNV virus-like particles (VLP) expressing the WNV M and E proteins. Immune equine F(ab′)2 fragments and immune horse sera efficiently neutralized WNV infection in tissue culture. The passive transfer of equine immune antibodies significantly accelerated the virus clearance in the spleens and brains of WNV infected mice, and reduced mortality. Thus, equine immunoglobulin or equine neutralizing F(ab′)2 passive immunotherapy is a potential strategy for the prophylactic or therapeutic treatment of patients infected with WNV. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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2778 KiB  
Article
Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models
by Rodrigo Delvecchio, Luiza M. Higa, Paula Pezzuto, Ana Luiza Valadão, Patrícia P. Garcez, Fábio L. Monteiro, Erick C. Loiola, André A. Dias, Fábio J. M. Silva, Matthew T. Aliota, Elizabeth A. Caine, Jorge E. Osorio, Maria Bellio, David H. O’Connor, Stevens Rehen, Renato Santana De Aguiar, Andrea Savarino, Loraine Campanati and Amilcar Tanuri
Viruses 2016, 8(12), 322; https://0-doi-org.brum.beds.ac.uk/10.3390/v8120322 - 29 Nov 2016
Cited by 221 | Viewed by 18003
Abstract
Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is [...] Read more.
Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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3490 KiB  
Article
Epitope Identification and Application for Diagnosis of Duck Tembusu Virus Infections in Ducks
by Chenxi Li, Junyan Liu, Wulin Shaozhou, Xiaofei Bai, Qingshan Zhang, Ronghong Hua, Jyung-Hurng Liu, Ming Liu and Yun Zhang
Viruses 2016, 8(11), 306; https://0-doi-org.brum.beds.ac.uk/10.3390/v8110306 - 10 Nov 2016
Cited by 12 | Viewed by 5576
Abstract
Duck Tembusu virus (DTMUV) causes substantial egg drop disease. DTMUV was first identified in China and rapidly spread to Malaysia and Thailand. The antigenicity of the DTMUV E protein has not yet been characterized. Here, we investigated antigenic sites on the E protein [...] Read more.
Duck Tembusu virus (DTMUV) causes substantial egg drop disease. DTMUV was first identified in China and rapidly spread to Malaysia and Thailand. The antigenicity of the DTMUV E protein has not yet been characterized. Here, we investigated antigenic sites on the E protein using the non-neutralizing monoclonal antibodies (mAbs) 1F3 and 1A5. Two minimal epitopes were mapped to 221LD/NLPW225 and 87YAEYI91 by using phage display and mutagenesis. DTMUV-positive duck sera reacted with the epitopes, thus indicating the importance of the minimal amino acids of the epitopes for antibody-epitope binding. The performance of the dot blotting assay with the corresponding positive sera indicated that YAEYI was DTMUV type-specific, whereas 221LD/NLPW225 was a cross-reactive epitope for West Nile virus (WNV), dengue virus (DENV), and Japanese encephalitis virus (JEV) and corresponded to conserved and variable amino acid sequences among these strains. The structure model of the E protein revealed that YAEYI and LD/NLPW were located on domain (D) II, which confirmed that DII might contain a type-specific non-neutralizing epitope. The YAEYI epitope-based antigen demonstrated its diagnostic potential by reacting with high specificity to serum samples obtained from DTMUV-infected ducks. Based on these observations, a YAEYI-based serological test could be used for DTMUV surveillance and could differentiate DTMUV infections from JEV or WNV infections. These findings provide new insights into the organization of epitopes on flavivirus E proteins that might be valuable for the development of epitope-based serological diagnostic tests for DTMUV. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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4661 KiB  
Article
4EBP-Dependent Signaling Supports West Nile Virus Growth and Protein Expression
by Katherine D. Shives, Aaron R. Massey, Nicholas A. May, Thomas E. Morrison and J. David Beckham
Viruses 2016, 8(10), 287; https://0-doi-org.brum.beds.ac.uk/10.3390/v8100287 - 18 Oct 2016
Cited by 7 | Viewed by 11728
Abstract
West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7GpppNm 5′ cap with 2′-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its [...] Read more.
West Nile virus (WNV) is a (+) sense, single-stranded RNA virus in the Flavivirus genus. WNV RNA possesses an m7GpppNm 5′ cap with 2′-O-methylation that mimics host mRNAs preventing innate immune detection and allowing the virus to translate its RNA genome through the utilization of cap-dependent translation initiation effectors in a wide variety of host species. Our prior work established the requirement of the host mammalian target of rapamycin complex 1 (mTORC1) for optimal WNV growth and protein expression; yet, the roles of the downstream effectors of mTORC1 in WNV translation are unknown. In this study, we utilize gene deletion mutants in the ribosomal protein kinase called S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein (4EBP) pathways downstream of mTORC1 to define the role of mTOR-dependent translation initiation signals in WNV gene expression and growth. We now show that WNV growth and protein expression are dependent on mTORC1 mediated-regulation of the eukaryotic translation initiation factor 4E-binding protein/eukaryotic translation initiation factor 4E-binding protein (4EBP/eIF4E) interaction and eukaryotic initiation factor 4F (eIF4F) complex formation to support viral growth and viral protein expression. We also show that the canonical signals of mTORC1 activation including ribosomal protein s6 (rpS6) and S6K phosphorylation are not required for WNV growth in these same conditions. Our data suggest that the mTORC1/4EBP/eIF4E signaling axis is activated to support the translation of the WNV genome. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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2516 KiB  
Communication
Analysis of the Langat Virus Genome in Persistent Infection of an Ixodes scapularis Cell Line
by Luwanika Mlera, Wessam Melik, Danielle K. Offerdahl, Eric Dahlstrom, Stephen F. Porcella and Marshall E. Bloom
Viruses 2016, 8(9), 252; https://0-doi-org.brum.beds.ac.uk/10.3390/v8090252 - 10 Sep 2016
Cited by 4 | Viewed by 6110
Abstract
Tick-borne flaviviruses (TBFVs) cause a broad spectrum of disease manifestations ranging from asymptomatic to mild febrile illness and life threatening encephalitis. These single-stranded positive-sense (ss(+)) RNA viruses are naturally maintained in a persistent infection of ixodid ticks and small-medium sized mammals. The development [...] Read more.
Tick-borne flaviviruses (TBFVs) cause a broad spectrum of disease manifestations ranging from asymptomatic to mild febrile illness and life threatening encephalitis. These single-stranded positive-sense (ss(+)) RNA viruses are naturally maintained in a persistent infection of ixodid ticks and small-medium sized mammals. The development of cell lines from the ixodid ticks has provided a valuable surrogate system for studying the biology of TBFVs in vitro. When we infected ISE6 cells, an Ixodes scapularis embryonic cell line, with Langat virus (LGTV) we observed that the infection proceeded directly into persistence without any cytopathic effect. Analysis of the viral genome at selected time points showed that no defective genomes were generated during LGTV persistence by 10 weeks of cell passage. This was in contrast to LGTV persistence in 293T cells in which defective viral genomes are detectable by five weeks of serial cell passage. We identified two synonymous nucleotide changes i.e., 1893A→C (29% of 5978 reads at 12 h post infection (hpi)) and 2284T→A (34% of 4191 reads at 12 hpi) in the region encoding for the viral protein E. These results suggested that the mechanisms supporting LGTV persistence are different between tick and mammalian cells. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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Review

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277 KiB  
Review
Zika Virus: Recent Advances towards the Development of Vaccines and Therapeutics
by Monica A. McArthur
Viruses 2017, 9(6), 143; https://0-doi-org.brum.beds.ac.uk/10.3390/v9060143 - 13 Jun 2017
Cited by 27 | Viewed by 9068
Abstract
Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In [...] Read more.
Zika is a rapidly emerging public health threat. Although clinical infection is frequently mild, significant neurological manifestations have been demonstrated in infants born to Zika virus (ZIKV) infected mothers. Due to the substantial ramifications of intrauterine infection, effective counter-measures are urgently needed. In order to develop effective anti-ZIKV vaccines and therapeutics, improved animal models and a better understanding of immunological correlates of protection against ZIKV are required. This review will summarize what is currently known about ZIKV, the clinical manifestations and epidemiology of Zika as well as, the development of animal models to study ZIKV infection, host immune responses against ZIKV, and the current state of development of vaccines and therapeutics against ZIKV. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
1282 KiB  
Review
Historical Perspectives on Flavivirus Research
by Michael R. Holbrook
Viruses 2017, 9(5), 97; https://0-doi-org.brum.beds.ac.uk/10.3390/v9050097 - 30 Apr 2017
Cited by 111 | Viewed by 16202
Abstract
The flaviviruses are small single-stranded RNA viruses that are typically transmitted by mosquito or tick vectors. These “arboviruses” are found around the world and account for a significant number of cases of human disease. The flaviviruses cause diseases ranging from mild or sub-clinical [...] Read more.
The flaviviruses are small single-stranded RNA viruses that are typically transmitted by mosquito or tick vectors. These “arboviruses” are found around the world and account for a significant number of cases of human disease. The flaviviruses cause diseases ranging from mild or sub-clinical infections to lethal hemorrhagic fever or encephalitis. In many cases, survivors of neurologic flavivirus infections suffer long-term debilitating sequelae. Much like the emergence of West Nile virus in the United States in 1999, the recent emergence of Zika virus in the Americas has significantly increased the awareness of mosquito-borne viruses. The diseases caused by several flaviviruses have been recognized for decades, if not centuries. However, there is still a lot that is unknown about the flaviviruses as the recent experience with Zika virus has taught us. The objective of this review is to provide a general overview and some historical perspective on several flaviviruses that cause significant human disease. In addition, available medical countermeasures and significant gaps in our understanding of flavivirus biology are also discussed. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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251 KiB  
Review
T Cell-Mediated Immunity towards Yellow Fever Virus and Useful Animal Models
by Alan M. Watson and William B. Klimstra
Viruses 2017, 9(4), 77; https://0-doi-org.brum.beds.ac.uk/10.3390/v9040077 - 11 Apr 2017
Cited by 25 | Viewed by 6668
Abstract
The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a [...] Read more.
The 17D line of yellow fever virus vaccines is among the most effective vaccines ever created. The humoral and cellular immunity elicited by 17D has been well characterized in humans. Neutralizing antibodies have long been known to provide protection against challenge with a wild-type virus. However, a well characterized T cell immune response that is robust, long-lived and polyfunctional is also elicited by 17D. It remains unclear whether this arm of immunity is protective following challenge with a wild-type virus. Here we introduce the 17D line of yellow fever virus vaccines, describe the current state of knowledge regarding the immunity directed towards the vaccines in humans and conclude with a discussion of animal models that are useful for evaluating T cell-mediated immune protection to yellow fever virus. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
1056 KiB  
Review
Non-Canonical Roles of Dengue Virus Non-Structural Proteins
by Julianna D. Zeidler, Lorena O. Fernandes-Siqueira, Glauce M. Barbosa and Andrea T. Da Poian
Viruses 2017, 9(3), 42; https://0-doi-org.brum.beds.ac.uk/10.3390/v9030042 - 13 Mar 2017
Cited by 24 | Viewed by 9284
Abstract
The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of [...] Read more.
The Flaviviridae family comprises a number of human pathogens, which, although sharing structural and functional features, cause diseases with very different outcomes. This can be explained by the plurality of functions exerted by the few proteins coded by viral genomes, with some of these functions shared among members of a same family, but others being unique for each virus species. These non-canonical functions probably have evolved independently and may serve as the base to the development of specific therapies for each of those diseases. Here it is discussed what is currently known about the non-canonical roles of dengue virus (DENV) non-structural proteins (NSPs), which may account for some of the effects specifically observed in DENV infection, but not in other members of the Flaviviridae family. This review explores how DENV NSPs contributes to the physiopathology of dengue, evasion from host immunity, metabolic changes, and redistribution of cellular components during infection. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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791 KiB  
Review
The IMPORTance of the Nucleus during Flavivirus Replication
by Adam J. Lopez-Denman and Jason M. Mackenzie
Viruses 2017, 9(1), 14; https://0-doi-org.brum.beds.ac.uk/10.3390/v9010014 - 19 Jan 2017
Cited by 32 | Viewed by 7517
Abstract
Flaviviruses are a large group of arboviruses of significant medical concern worldwide. With outbreaks a common occurrence, the need for efficient viral control is required more than ever. It is well understood that flaviviruses modulate the composition and structure of membranes in the [...] Read more.
Flaviviruses are a large group of arboviruses of significant medical concern worldwide. With outbreaks a common occurrence, the need for efficient viral control is required more than ever. It is well understood that flaviviruses modulate the composition and structure of membranes in the cytoplasm that are crucial for efficient replication and evading immune detection. As the flavivirus genome consists of positive sense RNA, replication can occur wholly within the cytoplasm. What is becoming more evident is that some viral proteins also have the ability to translocate to the nucleus, with potential roles in replication and immune system perturbation. In this review, we discuss the current understanding of flavivirus nuclear localisation, and the function it has during flavivirus infection. We also describe—while closely related—the functional differences between similar viral proteins in their nuclear translocation. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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Other

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164 KiB  
Commentary
The New High Resolution Crystal Structure of NS2B-NS3 Protease of Zika Virus
by Syed Lal Badshah, Abdul Naeem and Yahia Mabkhot
Viruses 2017, 9(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/v9010007 - 10 Jan 2017
Cited by 12 | Viewed by 6002
Abstract
Zika virus (ZIKV) is the cause of a significant viral disease affecting humans, which has spread throughout many South American countries and has also become a threat to Southeastern Asia. This commentary discusses the article “Crystal structure of unlinked NS2B-NS3 protease from Zika [...] Read more.
Zika virus (ZIKV) is the cause of a significant viral disease affecting humans, which has spread throughout many South American countries and has also become a threat to Southeastern Asia. This commentary discusses the article “Crystal structure of unlinked NS2B-NS3 protease from Zika virus” published recently in the journal Science by Zhang et al. of Nanyang Technological University, Singapore. They resolved a 1.58 Å resolution structure of the NS2B-NS3 protease of ZIKV and demonstrated how peptide and non-peptide inhibitors interact with this structure, along with the different conformational states that were observed. This protease crystal structure offers new opportunities for the design and development of novel antiviral drugs used for the treatment and control of ZIKV. Full article
(This article belongs to the Special Issue Advances in Flavivirus Research)
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