Research Article: West Nile and St. Louis encephalitis viral genetic determinants of avian host competence

Date Published: February 15, 2018

Publisher: Public Library of Science

Author(s): Payal D. Maharaj, Angela M. Bosco-Lauth, Stanley A. Langevin, Michael Anishchenko, Richard A. Bowen, William K. Reisen, Aaron C. Brault, William B. Messer. http://doi.org/10.1371/journal.pntd.0006302

Abstract: West Nile virus (WNV) and St. Louis encephalitis (SLEV) virus are enzootically maintained in North America in cycles involving the same mosquito vectors and similar avian hosts. However, these viruses exhibit dissimilar viremia and virulence phenotypes in birds: WNV is associated with high magnitude viremias that can result in mortality in certain species such as American crows (AMCRs, Corvus brachyrhynchos) whereas SLEV infection yields lower viremias that have not been associated with avian mortality. Cross-neutralization of these viruses in avian sera has been proposed to explain the reduced circulation of SLEV since the introduction of WNV in North America; however, in 2015, both viruses were the etiologic agents of concurrent human encephalitis outbreaks in Arizona, indicating the need to re-evaluate host factors and cross-neutralization responses as factors potentially affecting viral co-circulation. Reciprocal chimeric WNV and SLEV viruses were constructed by interchanging the pre-membrane (prM)-envelope (E) genes, and viruses subsequently generated were utilized herein for the inoculation of three different avian species: house sparrows (HOSPs; Passer domesticus), house finches (Haemorhous mexicanus) and AMCRs. Cross-protective immunity between parental and chimeric viruses were also assessed in HOSPs. Results indicated that the prM-E genes did not modulate avian replication or virulence differences between WNV and SLEV in any of the three avian species. However, WNV-prME proteins did dictate cross-protective immunity between these antigenically heterologous viruses. Our data provides further evidence of the important role that the WNV / SLEV viral non-structural genetic elements play in viral replication, avian host competence and virulence.

Partial Text: West Nile (WNV) and St. Louis encephalitis (SLEV) viruses are serologically related flaviviruses (Flavivirus; Flaviviridae) that enzootically circulate between Culex spp. mosquitoes and avian amplification hosts in North America with the potential to give rise to epidemics of human encephalitis [1]. West Nile virus is capable of eliciting extended, high-magnitude viremias and mortality in a wide range of avian species including house sparrows (HOSPs, Passer domesticus), house finches (HOFIs, Haemorhous mexicanus) and American crows (AMCRs, Corvus brachyrhynchos) [2, 3]. Additionally, HOSPs and HOFIs are both competent host species for SLEV in North America [4–6]; however, WNV and SLEV exhibit differential virulence and mortality phenotypes in these species [7, 8]. American crows are highly susceptible to WNV infection and can generate serum viremias in excess of 11 log10 PFU/mL sera [2]. Consequently, they have been utilized as a sentinel species to track the spread of the virus in North America [9]. In contrast, SLEV presents low-level viremias in a more restricted range of birds and has not been associated with mortality in adult birds [1]. Since its first identification in North America in 1999, WNV has expanded its geographic range and established enzootic transmission foci throughout the continent [10]. Concurrent with this introduction and subsequent geographic radiation of WNV, SLEV enzootic activity has waned despite the increased levels of arboviral surveillance precipitated by the WNV invasion [11].

Virulence differences between WNV and SLEV in avian hosts have been well documented [7, 16, 34–38]. Compared to SLEV, WNV elicits significantly higher viremias in a wide range of avian hosts [7, 15, 17, 34, 35, 39, 40]. Data from the present study further support these avian host competence associations, where WNV elicited significantly higher viremias than SLEV in HOSPs, HOFIs and AMCRs. Inoculations of AMCRs further demonstrated that certain avian hosts are extremely competent for WNV replication, but fail to generate a detectable SLEV viremia [6]. Although corvids likely amplify WNV to levels leading to outbreaks of human disease [41], they conversely may suppress SLEV activity by serving as dead end hosts for this virus.

Source:

http://doi.org/10.1371/journal.pntd.0006302