Innate immune control of West Nile virus infection.

Section of Infectious Diseases, Yale School of Medicine, New Haven, CT, USA.
Cellular Microbiology (Impact Factor: 4.82). 07/2011; 13(11):1648-58. DOI: 10.1111/j.1462-5822.2011.01649.x
Source: PubMed

ABSTRACT West Nile virus (WNV), from the Flaviviridae family, is a re-emerging zoonotic pathogen of medical importance. In humans, WNV infection may cause life-threatening meningoencephalitis or long-term neurologic sequelae. WNV is transmitted by Culex spp. mosquitoes and both the arthropod vector and the mammalian host are equipped with antiviral innate immune mechanisms sharing a common phylogeny. As far as the current evidence is able to demonstrate, mosquitoes primarily rely on RNA interference, Toll, Imd and JAK-STAT signalling pathways for limiting viral infection, while mammals are provided with these and other more complex antiviral mechanisms involving antiviral effectors, inflammatory mediators, and cellular responses triggered by highly specialized pathogen detection mechanisms that often resemble their invertebrate ancestry. This mini-review summarizes our current understanding of how the innate immune systems of the vector and the mammalian host react to WNV infection and shape its pathogenesis.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: West Nile virus (WNV) is a human pathogen of significant medical importance with close to 40,000 cases of encephalitis and more than 1,600 deaths reported in the US alone since its first emergence in New York in 1999. Previous studies identified a motif in the beginning of non-structural gene NS2A of encephalitic flaviviruses including WNV which induces programmed -1 ribosomal frameshift (PRF) resulting in production of an additional NS protein NS1'. We have previously demonstrated that mutant WNV with abolished PRF was attenuated in mice. Here we have extended our previous observations by showing that PRF does not appear to have a significant role in virus replication, virion formation, and viral spread in several cell lines in vitro. However, we have also shown that PRF induces an over production of structural proteins over non-structural proteins in virus-infected cells and that mutation abolishing PRF is present in ∼11% of the wild type virus population. In vivo experiments in house sparrows using wild type and PRF mutant of New York 99 strain of WNV viruses showed some attenuation for the PRF mutant virus. Moreover, PRF mutant of Kunjin strain of WNV showed significant decrease compared to wild type virus infection in dissemination of the virus from the midgut through the haemocoel, and ultimately the capacity of infected mosquitoes to transmit virus. Thus our results demonstrate an important role for PRF in regulating expression of viral genes and consequently virus replication in avian and mosquito hosts.
    PLoS Pathogens 11/2014; 10(11):e1004447. DOI:10.1371/journal.ppat.1004447 · 8.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: West Nile virus (WNV) is a mosquito-borne enveloped positive-strand RNA virus that emerged in North America in 1999 in New York City. Over the past 15 years, WNV has become established throughout the USA and has spread into Canada, Mexico and the Caribbean. CDC reports indicate >41,000 clinical cases, including more than 1700 fatalities. An estimated 3 million people in the USA may have been infected to date. Infection with WNV is dependent on many factors including climate, mosquito habitats and immunologically naïve bird populations. In addition, variations within individuals contribute to the risk of severe disease, in particular, advanced age, hypertension, immunosuppression and critical elements of the immune response. Recent advances in technology now allow detailed analysis of complex immune interactions relevant to disease susceptibility.
    Expert Review of Anti-infective Therapy 01/2015; DOI:10.1586/14787210.2015.1007043 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The Flavivirus genus is in the family Flaviviridae and is comprised of more than 70 viruses. These viruses have a broad geographic range, circulating on every continent except Antarctica. Mosquito-borne flaviviruses, such as yellow fever virus, dengue virus serotypes 1-4, Japanese encephalitis virus, and West Nile virus are responsible for significant human morbidity and mortality in affected regions. This review focuses on what is known about flavivirus-mosquito interactions and presents key data collected from the field and laboratory-based molecular and ultrastructural evaluations.
    Viruses 11/2014; 6(11):4703-4730. DOI:10.3390/v6114703 · 3.28 Impact Factor

Full-text (2 Sources)

Available from
May 29, 2014