Persistent Infection with West Nile Virus Years after Initial Infection

Murray, Kristy O.; Walker, Christopher M.; Herrington, Emily; Lewis, Jessica A.; McCormick, Joseph B.; Beasley, David W.C.; Tesh, Robert B.; Fisher‐Hoch, Susan P.

doi:10.1086/648731

Cited by 200 publications

(175 citation statements)

References 12 publications

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“…The purpose of this study was to explore the potential effect of synonymous codon usage bias in the beginning region of WNV and the tRNA concentrations for this region in the vector and dead-end host. Our observations indicated that some patients were persistently infected with WNV and that the kidney may be a preferred site of continued replication and source of shedding (Murray et al, 2010a), suggesting that codon usage in this virus may be influenced by its dead-end host. The significant increase in translation rate owing to the appropriate arrangement of codons has an important impact on how the translation machinery functions.…”

Section: Discussionmentioning

confidence: 77%

Characteristics of synonymous codon usage bias in the beginning region of West Nile virus

Ma¹,

Feng²,

Liu³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Adaptation in the overall codon usage pattern of West Nile virus (WNV) to that of two hosts was estimated based on the synonymous codon usage value (RSCU). Synonymous codon usage biases for the beginning coding sequence of this virus were also analyzed by calculating the usage fluctuation for each synonymous codon along the target region (the first 270 codon sites of the whole coding sequence of WNV). Adaptation of WNV to Anopheles gambiae regarding the overall codon usage revealed a mixture of synonymous codon usage patterns between this virus and its vector. Regarding the adaptation of WNV to its dead-end host and codon usage, although a mixture of overall codon usage patterns exists, the number of codons with reversed tendency codon usage is lower than that between the virus and its vector. In addition, some codons with low RSCU values for this virus are highly selected in the beginning translation region of WNV, while codons with low RSCU values in this region tend to pair with tRNAs present in low abundance in the host, suggesting that highly selected codons in a specific region in the beginning region of WNV are, to some degree, influenced by the corresponding low tRNA abundance of hosts to regulate the translation speed of the WNV polyprotein.

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Section: Discussionmentioning

confidence: 77%

Characteristics of synonymous codon usage bias in the beginning region of West Nile virus

Ma¹,

Feng²,

Liu³

et al. 2014

Genet. Mol. Res.

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“…In contrast to neurons and macrophages, these latter cells do not die following infection. Instead they survive and often become persistently infected (21,22,29). Consistent with these results, we show that in vitro infection of macrophages with either Dengue-2 or Modoc virus results in cell killing similar to that of CPT at 48 hpi, whereas infection with either virus fails to kill renal epithelial cells and fibroblasts (MDCK, 293T, Vero, SW primary MEF, and C57/Bl primary MEF) even when the cells are infected at extremely high titer (m.o.i.…”

Section: Discussionmentioning

confidence: 99%

Flavivirus NS4A-induced Autophagy Protects Cells against Death and Enhances Virus Replication

McLean

Wudzinska

Datan

et al. 2011

Journal of Biological Chemistry

230

223

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Over 2.5 billion people live in areas at high risk for Dengue and related flavivirus infections (1). Dengue hemorrhagic fever, a severe complication present in ϳ5% of cases, claims more lives annually than all other hemorrhagic fevers combined (2); much of the damage is caused by death of infected cells. The fate of infected cells depends on cell type. Although flavivirus induces apoptosis of neurons and macrophages, infected hepatocytes and epithelial cells do not die. We find that flavivirus up-regulates autophagy in MDCK 3 renal epithelial cells and other cell types and subsequently protects them. We further identify nonstructural protein NS4A of both Dengue-2 and Modoc viruses as the sole viral mediator of autophagy up-regulation and protection against death. Up-regulation of autophagosomes by either live virus infection or NS4A expression depends on PI3K and is important for replication of flavivirus in renal epithelial cells. Flaviviruses often persist in liver and kidney following the acute phase of infection, suggesting that infected cells evade destruction by the host immune response, likely by flavivirusinduced up-regulation of autophagy in these cells. In vitro infection of hepatocytes and fibroblasts leads to up-regulation in autophagy and protection against death (3, 4). More relevant, Dengue-2 viruses replicate within the hepatocyte autophagosomes (5), and inhibition of autophagy attenuates virus replication (3). We extend these findings by identifying the nonstructural viral protein NS4A as the virus-encoded protein that up-regulates autophagy and thus protects the host cell against death, providing a well protected host cell for long term replication of virus.The flavivirus genome contains 10 genes encoding an ϳ11-kDa polyprotein precursor that binds to the ER membrane after translation at the rough ER as follows: three structural proteins (capsid (core) protein, pre-membrane protein ,and envelope glycoprotein) and seven nonstructural genes (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) that mediate viral replication, assembly, and evasion of the host immune system. The active proteins are cleaved from the ER-bound viral polyprotein by cellular proteases signalase and furin and viral protease NS3/ 2B. NS3 is both a viral protease (with required cofactor NS2B (6)) and a viral ATP-dependent helicase (7, 8); NS5 is an RNAdependent RNA polymerase and methyltransferase (9) responsible for virus genome replication, whereas NS1 is possibly a part of the viral replication complex (10). The small hydrophobic flavivirus proteins (NS2A, NS4A, and NS4B) remain the most poorly characterized. NS2A is required for the assembly of new flavivirus virions; NS4A associates with the virus replication complex and induces ER membrane rearrangements (discussed below), and NS4B is an antagonist of interferon. Flavivirus NS4A is an ϳ16-kDa membrane-associated protein consisting of four transmembrane helices and an N-terminal cytosolic region. Once the viral genome is translated in the ER,

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“…Further, the large increase in the incidence of cases of WNV in North America registered in 2012 makes the possibility of further geographical expansion of the infection in Europe highly likely, under the influence of an expansion of the boundaries of competent vectors. Considering the possibility of chronic and persistent human infections (Murray et al, 2010) and the evidence of serious long-term sequelae in patients with a history of WNV infection (Nolan et al, 2012), it becomes apparent that WNV infection could have substantial public-health implications and emphasizes the importance of having surveillance systems monitoring the activity of WNV in humans, mosquitoes, birds and other animals.…”

mentioning

confidence: 99%

Heterogeneity of West Nile virus genotype 1a in Italy, 2011

Rossini

Carletti²,

Rigoli

et al. 2013

Journal of General Virology

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West Nile virus (WNV) is currently circulating in several European countries and, over recent decades, concomitantly with enhanced surveillance studies and improved diagnostic capabilities, an increase in the geographical distribution and in the number of cases in Europe has been documented. In Italy in 2011, 14 human cases of WNV neuroinvasive infections due to lineage 1 strains were registered in several Italian regions. Here we report WNV partial sequences obtained from serum samples of two patients living in different regions of Italy (Veneto and Sardinia). Phylogenetic analysis, performed on a fragment (566 nt) of the envelope gene, showed that WNV strains circulating in Italy in 2011 belong to lineage 1a, but are different from lineage 1a strains isolated in 2008–2009.The data reported here are consistent with the hypothesis of multiple recent introductions of WNV lineage 1a strains into Italy.

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Persistent Infection with West Nile Virus Years after Initial Infection

Cited by 200 publications

References 12 publications

Characteristics of synonymous codon usage bias in the beginning region of West Nile virus

Characteristics of synonymous codon usage bias in the beginning region of West Nile virus

Flavivirus NS4A-induced Autophagy Protects Cells against Death and Enhances Virus Replication

Heterogeneity of West Nile virus genotype 1a in Italy, 2011

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