The Alphaviruses are a group of related RNA viruses that are cyclically transmitted between mammalian / avian hosts and vector mosquitos. Members of the genus Alphavirus are recognized for their epidemic potential and several exhibit high mortality rates upon infection. Contemporary outbreaks of alphaviruses and the ongoing geographical distribution of vector-competent mosquitos towards naive populations underscore the need for effective antiviral targets and vaccine strategies. Previous studies have characterized alphaviral particles produced in mammalian and avian cells;however particles produced in mosquito cells have been largely overlooked. Examination of mosquito derived Sindbis virus (SINV) has indicated that host ribosomal components are incorporated into the viral particles. Characterization of this phenomenon revealed that host ribosomes are incorporated into mammalian derived particles as well, but at a rate less than that observed for mosquito derived particles. Interestingly, the levels of ribosome encapsidation were found to correlate with the number of infectious particles. The work detailed in this proposal uses a multidisciplinary approach consisting of virological, molecular, structural and model organism studies to characterize the determinants leading to and the biological role of ribosome encapsidation. This proposal is designed to provide a unique training experience that will enable those involved in its conceptualization and implementation to continue towards a career as an independent scientist.
Alphaviruses are recognized for recent epidemics and the potential severity of their impact on human health. This proposal seeks to identify and characterize features of the virus which enhance the infectivity of the virus in both mammalian and mosquito hosts. Increasing our understanding of the determinants behind the enhancement of infectivity will result in novel antiviral targets and potential vaccine development strategies.
|Rupp, Jonathan C; Sokoloski, Kevin J; Gebhart, Natasha N et al. (2015) Alphavirus RNA synthesis and non-structural protein functions. J Gen Virol 96:2483-500|
|Sokoloski, K J; Haist, K C; Morrison, T E et al. (2015) Noncapped Alphavirus Genomic RNAs and Their Role during Infection. J Virol 89:6080-92|
|Sokoloski, Kevin J; Snyder, Anthony J; Liu, Natalia H et al. (2013) Encapsidation of host-derived factors correlates with enhanced infectivity of Sindbis virus. J Virol 87:12216-26|