Massively Parallel Sequencing of FIV Reveals Compartmental Differences Among Tissues in Dual and Single Infections

• Activity Number: 246
• Type: Contributed
• Date/Time: Monday, August 5, 2013 : 2:00 PM to 3:50 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Yang Liu*+ and Francesca Chiaromonte and Howard Ross and Daniel Elleder and Mary Poss
• Companies: The Pennsylvania State University and Penn State University and University of Auckland and The Pennsylvania State University and The Pennsylvania State University
• Keywords: Rare Variants ; Error Correction ; Deconvolution ; Linear Mixed Model ; Next Generation Sequencing ; Virus Population Genetics

Abstract

Genetic diversity accrues rapidly as RNA viruses replicate within a host and can be used to determine viral dynamics in response to treatment regimens. We previously showed that disease caused by a virulent strain of feline immunodeficiency virus (FIV) is less severe if cats are co-infected with a competing FIV strain. Virus population genetics can inform on mechanisms associated with protection from disease. We tested the hypothesis that the tissue specific replication of virulent FIV is altered in dual infection by employing massively parallel sequencing of the viral genome. Because rare variants dominate the virus population in tissues, our analysis required that genetic variation be distinguished from errors due to experimental protocols and the sequencing technology. To address this challenge, we adapted to our sequencing data a normalization approach based on an Exponential-Gaussian convolution model. We then applied to the resulting error-adjusted substitution frequencies an analysis of variance (ANOVA) based on a linear mixed model. The ANOVA revealed that the FIV dynamics differ among tissues in the presence and absence of a co-infecting virus.