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Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection
Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA
School of Biological Sciences, University of Auckland, Auckland, 1142, New Zealand
Department of Microbiology, Immunology, and Pathology, Colorado State University, Ft. Collins, CO 80523, USA
Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA
208 Mueller Lab, Center for Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA 16802, USA
* Author to whom correspondence should be addressed.
Received: 9 November 2010; in revised form: 25 November 2010 / Accepted: 29 November 2010 / Published: 10 December 2010
Abstract: CD4 decline is a hallmark of disease onset in individuals infected with Feline Immunodeficiency Virus (FIV) or Human Immunodeficiency Virus type 1 (HIV-1). Cats that are infected with a poorly replicating, apathogenic FIV (PLV) prior to exposure to a virulent FIV strain (FIVC) maintain CD4 numbers by mechanisms that are not correlated with a measurable adaptive immune response or reduction in circulating viral load. We employed population genetic approaches based on the 3' portion of the viral genome to estimate the population structure of FIVC from single and dual infected cats. In dual infected cats, FIVC effective population size was decreased during the initial viral expansion phase, and after three weeks of infection, the population declined sharply. The FIVC population recovered to pre-bottleneck levels approximately seven weeks post-FIVC infection. However, the population emerging from the bottleneck in dual infected cats was distinct based on estimates of temporal population structure and substitution profiles. The transition to transversion rate ratio (k) increased from early to late phases in dual infected cats due primarily to a decrease in transversions whereas in single infected cats, k declined over time. Although one clone with extensive G to A substitutions, indicative of host cytidine deaminase editing, was recovered from a dual infected cat during the bottleneck, the post bottleneck population had an overall reduction in G to A substitutions. These data are consistent with a model of PLV-induced host restriction, putatively involving host DNA editing, that alters the dynamics of FIVC throughout the course of infection leading to disease attenuation.
Keywords: Lentivirus; dual infection; population genetics; genetic bottleneck; viral temporal dynamics; mutation rate
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Padhi, A.; Ross, H.; Terwee, J.; VandeWoude, S.; Poss, M. Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection. Viruses 2010, 2, 2663-2680.
Padhi A, Ross H, Terwee J, VandeWoude S, Poss M. Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection. Viruses. 2010; 2(12):2663-2680.
Padhi, Abinash; Ross, Howard; Terwee, Julie; VandeWoude, Sue; Poss, Mary. 2010. "Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection." Viruses 2, no. 12: 2663-2680.