scholarly journals Viral envelope protein glycosylation is a molecular determinant of the neuroinvasiveness of the New York strain of West Nile virus

2004 ◽  
Vol 85 (12) ◽  
pp. 3637-3645 ◽  
Author(s):  
Kazuya Shirato ◽  
Hirotsugu Miyoshi ◽  
Akiko Goto ◽  
Yoshihiko Ako ◽  
Tomotaka Ueki ◽  
...  
Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 493 ◽  
Author(s):  
Helge Kampen ◽  
Cora M. Holicki ◽  
Ute Ziegler ◽  
Martin H. Groschup ◽  
Birke Andrea Tews ◽  
...  

In 2018, West Nile virus (WNV) broke out for the first time in Germany, with continuation of the epidemic in 2019, involving birds, horses and humans. To identify vectors and characterize the virus, mosquitoes were collected in both years in zoological gardens and on a horse meadow immediately following the diagnosis of disease cases in birds and horses. Mosquitoes were identified and screened for WNV by qRT-PCR, with virus-positive samples being sequenced for the viral envelope protein gene. While no positive mosquitoes were found in 2018, seven mosquito pools tested positive for WNV in 2019 in the Tierpark (Wildlife Park) Berlin. The pools consisted of Cx. pipiens biotype pipiens (n = 5), and a mixture of Cx. p. biotype pipiens and Cx. p. biotype molestus (n = 2), or hybrids of these, and were collected between 13 August and 24 September 2019. The virus strain turned out to be nearly identical to two WNV strains isolated from birds diseased in 2018 in eastern Germany. The findings represent the first demonstration of WNV in mosquitoes in Germany and include the possibility of local overwintering of the virus.


Virology ◽  
2008 ◽  
Vol 373 (2) ◽  
pp. 322-328 ◽  
Author(s):  
Markus Vossmann ◽  
Martin Kirst ◽  
Diana Ludolfs ◽  
Michael Schreiber

2006 ◽  
Vol 81 (4) ◽  
pp. 2047-2055 ◽  
Author(s):  
Fengwei Bai ◽  
Terrence Town ◽  
Deepti Pradhan ◽  
Jonathan Cox ◽  
Ashish ◽  
...  

ABSTRACT West Nile virus (WNV) can cause fatal murine and human encephalitis. The viral envelope protein interacts with host cells. A murine brain cDNA phage display library was therefore probed with WNV envelope protein, resulting in the identification of several adherent peptides. Of these, peptide 1 prevented WNV infection in vitro with a 50% inhibition concentration of 67 μM and also inhibited infection of a related flavivirus, dengue virus. Peptide 9, a derivative of peptide 1, was a particularly potent inhibitor of WNV in vitro, with a 50% inhibition concentration of 2.6 μM. Moreover, mice challenged with WNV that had been incubated with peptide 9 had reduced viremia and fatality compared with control animals. Peptide 9 penetrated the murine blood-brain barrier and was found in the brain parenchyma, implying that it may have antiviral activity in the central nervous system. These short peptides serve as the basis for developing new therapeutics for West Nile encephalitis and, potentially, other flaviviruses.


Virology ◽  
2009 ◽  
Vol 387 (1) ◽  
pp. 222-228 ◽  
Author(s):  
Robin M. Moudy ◽  
Bo Zhang ◽  
Pei-Yong Shi ◽  
Laura D. Kramer

2004 ◽  
Vol 279 (37) ◽  
pp. 38755-38761 ◽  
Author(s):  
David E. Volk ◽  
David W. C. Beasley ◽  
Deborah A. Kallick ◽  
Michael R. Holbrook ◽  
Alan D. T. Barrett ◽  
...  

2008 ◽  
Vol 89 (3) ◽  
pp. 627-635 ◽  
Author(s):  
Thomas J. Chambers ◽  
Deborah A. Droll ◽  
Andrew H. Walton ◽  
Julie Schwartz ◽  
William S. M. Wold ◽  
...  

The attenuated West Nile virus 25A strain (WN25A) was investigated for its neuroinvasive properties in B-cell-deficient (μMT) mice. After peripheral inoculation, WN25A caused fatal encephalitis in the majority of 6–8-week-old mice, characterized by a systemic infection with viraemia, moderate virus burdens in peripheral tissues and a high titre of brain-associated virus. Mice generally succumbed to infection within a few weeks of infection. However, others survived for as long as 10 weeks, and some for even longer. Normal age-matched C57BL/6 mice showed no signs of illness after inoculation with WN25A virus. Nucleotide sequencing of WN25A viruses recovered from the brains of B-cell-deficient mice revealed that the conserved N-linked glycosylation site in the viral envelope protein was abolished by substitution of a serine residue at position 155. This was found to be a pseudoreversion relative to the wild-type WN-Israel strain, based on virulence testing of one such brain-associated virus in both B-cell-deficient and normal C57BL/6 mice. This study provides further characterization of the mouse virulence properties of the attenuated WN25A virus in the context of B-cell deficiency. Replication in these mice does not involve rapid neuroadaptation or reversion of WN25A virus to a neuroinvasive phenotype. Molecular modelling studies suggest a difference in local structure of the E protein associated with either an asparagine or serine residue at position 155 compared with the tyrosine found in the virulent parental WN-Israel virus.


2002 ◽  
Vol 76 (24) ◽  
pp. 13097-13100 ◽  
Author(s):  
David W. C. Beasley ◽  
Alan D. T. Barrett

ABSTRACT Using a panel of neutralizing monoclonal antibodies, we have mapped epitopes in domain III of the envelope protein of the New York strain of West Nile virus. The ability of monoclonal antibodies that recognize these epitopes to neutralize virus appeared to differ between lineage I and II West Nile virus strains, and epitopes were located on the upper surface of domain III at residues E307, E330, and E332.


2005 ◽  
Vol 79 (13) ◽  
pp. 8339-8347 ◽  
Author(s):  
David W. C. Beasley ◽  
Melissa C. Whiteman ◽  
Shuliu Zhang ◽  
Claire Y.-H. Huang ◽  
Bradley S. Schneider ◽  
...  

ABSTRACT The introduction of West Nile virus (WNV) into North America has been associated with relatively high rates of neurological disease and death in humans, birds, horses, and some other animals. Previous studies identified strains in both genetic lineage 1 and genetic lineage 2, including North American isolates of lineage 1, that were highly virulent in a mouse neuroinvasion model, while other strains were avirulent or significantly attenuated (D. W. C. Beasley, L. Li, M. T. Suderman, and A. D. T. Barrett, Virology 296:17-23, 2002). To begin to elucidate the basis for these differences, we compared a highly virulent New York 1999 (NY99) isolate with a related Old World lineage 1 strain, An4766 (ETH76a), which is attenuated for mouse neuroinvasion. Genomic sequencing of ETH76a revealed a relatively small number of nucleotide (5.1%) and amino acid (0.6%) differences compared with NY99. These differences were located throughout the genome and included five amino acid differences in the envelope protein gene. Substitution of premembrane and envelope genes of ETH76a into a NY99 infectious clone backbone yielded a virus with altered in vitro growth characteristics and a mouse virulence phenotype comparable to ETH76a. Further site-specific mutagenesis studies revealed that the altered phenotype was primarily mediated via loss of envelope protein glycosylation and that this was associated with altered stability of the virion at mildly acidic pH. Therefore, the enhanced virulence of North American WNV strains compared with other Old World lineage 1 strains is at least partly mediated by envelope protein glycosylation.


2009 ◽  
Vol 183 (1) ◽  
pp. 650-660 ◽  
Author(s):  
Hameeda Sultana ◽  
Harald G. Foellmer ◽  
Girish Neelakanta ◽  
Theodore Oliphant ◽  
Michael Engle ◽  
...  

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