scholarly journals Genetic variation in West Nile virus from naturally infected mosquitoes and birds suggests quasispecies structure and strong purifying selection

2005 ◽  
Vol 86 (8) ◽  
pp. 2175-2183 ◽  
Author(s):  
Greta Jerzak ◽  
Kristen A. Bernard ◽  
Laura D. Kramer ◽  
Gregory D. Ebel

Intrahost genetic diversity was analysed in naturally infected mosquitoes and birds to determine whether West Nile virus (WNV) exists in nature as a quasispecies and to quantify selective pressures within and between hosts. WNV was sampled from ten infected birds and ten infected mosquito pools collected on Long Island, NY, USA, during the peak of the 2003 WNV transmission season. A 1938 nt fragment comprising the 3′ 1159 nt of the WNV envelope (E) coding region and the 5′ 779 nt of the non-structural protein 1 (NS1) coding region was amplified and cloned and 20 clones per specimen were sequenced. Results from this analysis demonstrate that WNV infections are derived from a genetically diverse population of genomes in nature. The mean nucleotide diversity was 0·016 % within individual specimens and the mean percentage of clones that differed from the consensus sequence was 19·5 %. WNV sequences in mosquitoes were significantly more genetically diverse than WNV in birds. No host-dependent bias for particular types of mutations was observed and estimates of genetic diversity did not differ significantly between E and NS1 coding sequences. Non-consensus clones obtained from two avian specimens had highly similar genetic signatures, providing preliminary evidence that WNV genetic diversity may be maintained throughout the enzootic transmission cycle, rather than arising independently during each infection. Evidence of purifying selection was obtained from both intra- and interhost WNV populations. Combined, these data support the observation that WNV populations may be structured as a quasispecies and document strong purifying natural selection in WNV populations.

2004 ◽  
Vol 78 (21) ◽  
pp. 11605-11614 ◽  
Author(s):  
Frank Scholle ◽  
Yvette A. Girard ◽  
Qizu Zhao ◽  
Stephen Higgs ◽  
Peter W. Mason

ABSTRACT A trans-packaging system for West Nile virus (WNV) subgenomic replicon RNAs (repRNAs), deleted for the structural coding region, was developed. WNV repRNAs were efficiently encapsidated by the WNV C/prM/E structural proteins expressed in trans from replication-competent, noncytopathic Sindbis virus-derived RNAs. Infectious virus-like particles (VLPs) were produced in titers of up to 109 infectious units/ml. WNV VLPs established a single round of infection in a variety of different cell lines without production of progeny virions. The infectious properties of WNV and VLPs were indistinguishable when efficiencies of infection of a number of different cell lines and inhibition of infection by neutralizing antibodies were determined. To investigate the usefulness of VLPs to address biological questions in vivo, Culex pipiens quinquefasciatus mosquitoes were orally and parenterally infected with VLPs, and dissected tissues were analyzed for WNV antigen expression. Antigen-positive cells in midguts of orally infected mosquitoes were detected as early as 2 days postinfection and as late as 8 days. Intrathoracic inoculation of VLPs into mosquitoes demonstrated a dose-dependent pattern of infection of secondary tissues and identified fat body, salivary glands, tracheal cells, and midgut muscle as susceptible WNV VLP infection targets. These results demonstrate that VLPs can serve as a valuable tool for the investigation of tissue tropism during the early stages of infection, where virus spread and the need for biosafety level 3 containment complicate the use of wild-type virus.


2006 ◽  
Vol 81 (5) ◽  
pp. 2531-2534 ◽  
Author(s):  
Katherine W. Snapinn ◽  
Edward C. Holmes ◽  
David S. Young ◽  
Kristen A. Bernard ◽  
Laura D. Kramer ◽  
...  

ABSTRACT To determine the demographic history of West Nile virus (WNV) in North America, we employed a coalescent method to envelope coding region data sets for the NY99 and WN02 genotypes. Although the observed genetic diversities in both genotypes were of approximately the same age, the mean rate of epidemiological growth of the WN02 population was approximately three times that of the NY99 population, a finding compatible with the recent dominance of the former genotype. However, there has also been a marked decrease in the recent growth rate of WN02, suggesting that WNV has reached its peak prevalence in North America.


Virology ◽  
2008 ◽  
Vol 374 (2) ◽  
pp. 256-260 ◽  
Author(s):  
Greta V.S. Jerzak ◽  
Ivy Brown ◽  
Pei-Yong Shi ◽  
Laura D. Kramer ◽  
Gregory D. Ebel

2019 ◽  
Vol 56 (6) ◽  
pp. 1467-1474 ◽  
Author(s):  
Nisha K Duggal ◽  
Kate E Langwig ◽  
Gregory D Ebel ◽  
Aaron C Brault

Abstract West Nile virus (WNV) was first identified in North America almost 20 yr ago. In that time, WNV has crossed the continent and established enzootic transmission cycles, resulting in intermittent outbreaks of human disease that have largely been linked with climatic variables and waning avian seroprevalence. During the transcontinental dissemination of WNV, the original genotype has been displaced by two principal extant genotypes which contain an envelope mutation that has been associated with enhanced vector competence by Culex pipiens L. (Diptera: Culicidae) and Culex tarsalis Coquillett vectors. Analyses of retrospective avian host competence data generated using the founding NY99 genotype strain have demonstrated a steady reduction in viremias of house sparrows over time. Reciprocally, the current genotype strains WN02 and SW03 have demonstrated an inverse correlation between house sparrow viremia magnitude and the time since isolation. These data collectively indicate that WNV has evolved for increased avian viremia while house sparrows have evolved resistance to the virus such that the relative host competence has remained constant. Intrahost analyses of WNV evolution demonstrate that selection pressures are avian species-specific and purifying selection is greater in individual birds compared with individual mosquitoes, suggesting that the avian adaptive and/or innate immune response may impose a selection pressure on WNV. Phylogenomic, experimental evolutionary systems, and models that link viral evolution with climate, host, and vector competence studies will be needed to identify the relative effect of different selective and stochastic mechanisms on viral phenotypes and the capacity of newly evolved WNV genotypes for transmission in continuously changing landscapes.


2015 ◽  
Vol 370 (1665) ◽  
pp. 20130561 ◽  
Author(s):  
Shlomit Paz

West Nile virus (WNV), the most widely distributed virus of the encephalitic flaviviruses, is a vector-borne pathogen of global importance. The transmission cycle exists in rural and urban areas where the virus infects birds, humans, horses and other mammals. Multiple factors impact the transmission and distribution of WNV, related to the dynamics and interactions between pathogen, vector, vertebrate hosts and environment. Hence, among other drivers, weather conditions have direct and indirect influences on vector competence (the ability to acquire, maintain and transmit the virus), on the vector population dynamic and on the virus replication rate within the mosquito, which are mostly weather dependent. The importance of climatic factors (temperature, precipitation, relative humidity and winds) as drivers in WNV epidemiology is increasing under conditions of climate change. Indeed, recent changes in climatic conditions, particularly increased ambient temperature and fluctuations in rainfall amounts, contributed to the maintenance (endemization process) of WNV in various locations in southern Europe, western Asia, the eastern Mediterranean, the Canadian Prairies, parts of the USA and Australia. As predictions show that the current trends are expected to continue, for better preparedness, any assessment of future transmission of WNV should take into consideration the impacts of climate change.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Melissa S. Nolan ◽  
Ana Zangeneh ◽  
Salma A. Khuwaja ◽  
Diana Martinez ◽  
Susan N. Rossmann ◽  
...  

West Nile virus (WNV), a mosquito-borne virus, has clinically affected hundreds of residents in the Houston metropolitan area since its introduction in 2002. This study aimed to determine if living within close proximity to a water source increases one’s odds of infection with WNV. We identified 356 eligible WNV-positive cases and 356 controls using a population proportionate to size model with US Census Bureau data. We found that living near slow moving water sources was statistically associated with increased odds for human infection, while living near moderate moving water systems was associated with decreased odds for human infection. Living near bayous lined with vegetation as opposed to concrete also showed increased risk of infection. The habitats of slow moving and vegetation lined water sources appear to favor the mosquito-human transmission cycle. These methods can be used by resource-limited health entities to identify high-risk areas for arboviral disease surveillance and efficient mosquito management initiatives.


Author(s):  
José F. Téllez-Zenteno ◽  
Gary Hunter ◽  
Lizbeth Hernández-Ronquillo ◽  
Edrish Haghir

Abstract:Background:West Nile virus (WNV) is a virus of the family Flaviviridae. The main route of human infection is through the bite of an infected mosquito. Approximately 90% of WNV infections in humans are asymptomatic, but neurologic manifestations can be severe.Methods:This study reviews the clinical profile of cases with neuroinvasive West Nile infection (NWNI) reported by the Surveillance program of the government of Saskatchewan in the Saskatoon Health Region (SHR). In 2007, 1456 cases of human West Nile cases were reported by the government of Saskatchewan in the whole province. One hundred and thirteen cases had severe symptoms of NWNI (8%), 1172 (80%) cases had mild symptoms of WNI and 171 (12%) had asymptomatic disease. Three hundred and fifty six cases were reported in the SHR, where 57 (16%) fulfilled criteria for NWNI.Results:From the 57 cases, 39 (68%) were females. Nine (16%) patients had a history of recent camping, two (4%) reported outdoor sports and four (8%) reported outdoor activities not otherwise specified. Twenty five patients had headache (43.9%), 25 confusion (42.1%), 23 meningitis (40.4%), 17 encephalitis (29.8%), 14 encephalopathy (24.6%), 11 meningoencephalitis (19.3%), 10 tremor (17.5%), acute flaccid paralysis 10 (17.5%), myoclonus 1 (1.8%), nystagmus 2 (3.5%), diplopia 2 (3.5%), dizziness 2 (3.5%). Three patients died related with comorbidities during admission.Conclusion:During a year of high occurrence of WNI in Saskatchewan, 16% of cases developed NWNI. The recognition of neurological complications associated with WNI is important to improve their referral to tertiary centers.


mBio ◽  
2015 ◽  
Vol 6 (3) ◽  
Author(s):  
Jessica B. Graham ◽  
Sunil Thomas ◽  
Jessica Swarts ◽  
Aimee A. McMillan ◽  
Martin T. Ferris ◽  
...  

ABSTRACT West Nile virus (WNV) is an emerging neuroinvasive flavivirus that now causes significant morbidity and mortality worldwide. The innate and adaptive immune responses to WNV infection have been well studied in C57BL/6J inbred mice, but this model lacks the variations in susceptibility, immunity, and outcome to WNV infection that are observed in humans, thus limiting its usefulness to understand the mechanisms of WNV infection and immunity dynamics. To build a model of WNV infection that captures human infection outcomes, we have used the Collaborative Cross (CC) mouse model. We show that this model, which recapitulates the genetic diversity of the human population, demonstrates diversity in susceptibility and outcomes of WNV infection observed in humans. Using multiple F1 crosses of CC mice, we identified a wide range of susceptibilities to infection, as demonstrated through differences in survival, clinical disease score, viral titer, and innate and adaptive immune responses in both peripheral tissues and the central nervous system. Additionally, we examined the Oas1b alleles in the CC mice and confirmed the previous finding that Oas1b plays a role in susceptibility to WNV; however, even within a given Oas1b allele status, we identified a wide range of strain-specific WNV-associated phenotypes. These results confirmed that the CC model is effective for identifying a repertoire of host genes involved in WNV resistance and susceptibility. The CC effectively models a wide range of WNV clinical, virologic, and immune phenotypes, thus overcoming the limitations of the traditional C57BL/6J model, allowing genetic and mechanistic studies of WNV infection and immunity in differently susceptible populations. IMPORTANCE Mouse models of West Nile virus infection have revealed important details regarding the innate and adaptive immune responses to this emerging viral infection. However, traditional mouse models lack the genetic diversity present in human populations and therefore limit our ability to study various disease outcomes and immunologic mechanisms subsequent to West Nile virus infection. In this study, we used the Collaborative Cross mouse model to more effectively model the wide range of clinical, virologic, and immune phenotypes present upon West Nile virus infection in humans.


PLoS ONE ◽  
2014 ◽  
Vol 9 (10) ◽  
pp. e108623 ◽  
Author(s):  
Xi-Xia Ding ◽  
Xiao-Feng Li ◽  
Yong-Qiang Deng ◽  
Yong-Hui Guo ◽  
Wei Hao ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e56534 ◽  
Author(s):  
Jody Hobson-Peters ◽  
Alice Wei Yee Yam ◽  
Jennifer Wei Fei Lu ◽  
Yin Xiang Setoh ◽  
Fiona J. May ◽  
...  

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