Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection

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 b...

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Main Authors: Abinash Padhi, Howard Ross, Julie Terwee, Mary Poss, Sue VandeWoude
Format: Article
Language:English
Published: MDPI AG 2010-12-01
Series:Viruses
Subjects:
Online Access:http://www.mdpi.com/1999-4915/2/12/2663/
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spelling doaj-f0f19becc8c04eb394146b8430fb5f6d2020-11-24T23:10:24ZengMDPI AGViruses1999-49152010-12-012122663268010.3390/v2122663Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus CoinfectionAbinash PadhiHoward RossJulie TerweeMary PossSue VandeWoudeCD4 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. http://www.mdpi.com/1999-4915/2/12/2663/Lentivirusdual infectionpopulation geneticsgenetic bottleneckviral temporal dynamicsmutation rate
collection DOAJ
language English
format Article
sources DOAJ
author Abinash Padhi
Howard Ross
Julie Terwee
Mary Poss
Sue VandeWoude
spellingShingle Abinash Padhi
Howard Ross
Julie Terwee
Mary Poss
Sue VandeWoude
Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection
Viruses
Lentivirus
dual infection
population genetics
genetic bottleneck
viral temporal dynamics
mutation rate
author_facet Abinash Padhi
Howard Ross
Julie Terwee
Mary Poss
Sue VandeWoude
author_sort Abinash Padhi
title Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection
title_short Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection
title_full Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection
title_fullStr Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection
title_full_unstemmed Profound Differences in Virus Population Genetics Correspond to Protection from CD4 Decline Resulting from Feline Lentivirus Coinfection
title_sort profound differences in virus population genetics correspond to protection from cd4 decline resulting from feline lentivirus coinfection
publisher MDPI AG
series Viruses
issn 1999-4915
publishDate 2010-12-01
description 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.
topic Lentivirus
dual infection
population genetics
genetic bottleneck
viral temporal dynamics
mutation rate
url http://www.mdpi.com/1999-4915/2/12/2663/
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