RNA viruses do not exist in nature as a single genomic sequence, but rather as an amalgam of related sequences referred to as a viral swarm or quasispecies. This proposal is designed to characterize the functional consequences of virus sequence variation within hosts that vary in immunological competence using WNV as a model. This proposal aims to identify how the type I IFN response differentially restricts viral growth an disease caused by a genetically homogenous versus heterogeneous virus population. It also addresses the effect of type I IFN on the evolution of the WNV genome, leading to a better understanding of the viral sequences and diversity (both nucleotide and protein) that are restricted by the type I IFN signaling pathway. A greater understanding of the interactions between type I IFN and a viral swarm could promote novel strategies to limit viral diversity, immune escape, and disease severity. In addition, understanding how type I IFN controls viral evolution could promote increased safety and immunogenicity of live attenuated vaccines, as most vaccines are derived from infectious clones, a source of homogenous virus.

Public Health Relevance

RNA viruses do not exist as a homogeneous entity but rather are a heterogeneous mixture, called a viral swarm. The diversity in a viral swarm is thought to be one factor that contributes to enhanced disease severity after infection. This project evaluates the role of one component of the innate immune system (interferon pathway) in controlling the disease severity induced by viral diversity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Career Transition Award (K22)
Project #
5K22AI104794-02
Application #
9207426
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID-B)
Program Officer
Repik, Patricia M
Project Start
2016-02-01
Project End
2018-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
2
Fiscal Year
2017
Total Cost
$108,000
Indirect Cost
$8,000
Name
Saint Louis University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
050220722
City
Saint Louis
State
MO
Country
United States
Zip Code
63103
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Pantoja, Petraleigh; Pérez-Guzmán, Erick X; Rodríguez, Idia V et al. (2017) Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus. Nat Commun 8:15674