Genetic diversity in the env V1-V2 region of proviral quasispecies from long-term controller MHC-typed cynomolgus macaques infected with SHIVSF162P4cy

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Abstract

Intra-host evolution of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) has been shown by viral RNA analysis in subjects who naturally suppress plasma viremia to low levels, known as controllers. However, little is known about the variability of proviral DNA and the inter-relationships among contained systemic viremia, rate of reservoir reseeding and specific major histocompatibility complex (MHC) genotypes, in controllers. Here, we analysed the proviral DNA quasispecies of the env V1-V2 region, in PBMCs and in anatomical compartments of 13 long-term controller monkeys after 3.2 years of infection with simian/human immunodeficiency virus (SHIV)SF162P4cy. A considerable variation in the genetic diversity of proviral quasispecies was present among animals. Seven monkeys exhibited env V1-V2 proviral populations composed of both clusters of identical ancestral sequences and new variants, whereas the other six monkeys displayed relatively high env V1-V2 genetic diversity with a large proportion of diverse novel sequences. Our results demonstrate that in SHIVSF162P4cy-infected monkeys there exists a disparate pattern of intra-host viral diversity and that reseeding of the proviral reservoir occurs in some animals. Moreover, even though no particular association has been observed between MHC haplotypes and the long-term control of infection, a remarkably similar pattern of intra-host viral diversity and divergence was found within animals carrying the M3 haplotype. This suggests that in animals bearing the same MHC haplotype and infected with the same virus, viral diversity follows a similar pattern with similar outcomes and control of infection.

Original languageEnglish
Article number001159
Pages (from-to)1717-1728
Number of pages12
JournalJournal of General Virology
Volume99
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

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Macaca
Major Histocompatibility Complex
Haplorhini
Haplotypes
Simian Immunodeficiency Virus
Viremia
Infection Control
HIV
DNA
Viral RNA
Genotype
Viruses
Infection
Population

Keywords

  • Diversity
  • Evolution
  • MCM
  • MHC
  • SHIV
  • Viremic controllers

ASJC Scopus subject areas

  • Virology

Cite this

@article{1dc0139a35934b7898cc35b657b411bf,
title = "Genetic diversity in the env V1-V2 region of proviral quasispecies from long-term controller MHC-typed cynomolgus macaques infected with SHIVSF162P4cy",
abstract = "Intra-host evolution of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) has been shown by viral RNA analysis in subjects who naturally suppress plasma viremia to low levels, known as controllers. However, little is known about the variability of proviral DNA and the inter-relationships among contained systemic viremia, rate of reservoir reseeding and specific major histocompatibility complex (MHC) genotypes, in controllers. Here, we analysed the proviral DNA quasispecies of the env V1-V2 region, in PBMCs and in anatomical compartments of 13 long-term controller monkeys after 3.2 years of infection with simian/human immunodeficiency virus (SHIV)SF162P4cy. A considerable variation in the genetic diversity of proviral quasispecies was present among animals. Seven monkeys exhibited env V1-V2 proviral populations composed of both clusters of identical ancestral sequences and new variants, whereas the other six monkeys displayed relatively high env V1-V2 genetic diversity with a large proportion of diverse novel sequences. Our results demonstrate that in SHIVSF162P4cy-infected monkeys there exists a disparate pattern of intra-host viral diversity and that reseeding of the proviral reservoir occurs in some animals. Moreover, even though no particular association has been observed between MHC haplotypes and the long-term control of infection, a remarkably similar pattern of intra-host viral diversity and divergence was found within animals carrying the M3 haplotype. This suggests that in animals bearing the same MHC haplotype and infected with the same virus, viral diversity follows a similar pattern with similar outcomes and control of infection.",
keywords = "Diversity, Evolution, MCM, MHC, SHIV, Viremic controllers",
author = "Alessia Capone and {Lo Presti}, Alessandra and Leonardo Sernicola and Stefania Farcomeni and Flavia Ferrantelli and Maggiorella, {Maria T.} and Mee, {Edward T.} and Rose, {Nicola J.} and Eleonora Cella and Massimo Ciccozzi and Barbara Ensoli and Alessandra Borsetti",
year = "2018",
month = "12",
day = "1",
doi = "10.1099/jgv.0.001159",
language = "English",
volume = "99",
pages = "1717--1728",
journal = "Journal of General Virology",
issn = "0022-1317",
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TY - JOUR

T1 - Genetic diversity in the env V1-V2 region of proviral quasispecies from long-term controller MHC-typed cynomolgus macaques infected with SHIVSF162P4cy

AU - Capone, Alessia

AU - Lo Presti, Alessandra

AU - Sernicola, Leonardo

AU - Farcomeni, Stefania

AU - Ferrantelli, Flavia

AU - Maggiorella, Maria T.

AU - Mee, Edward T.

AU - Rose, Nicola J.

AU - Cella, Eleonora

AU - Ciccozzi, Massimo

AU - Ensoli, Barbara

AU - Borsetti, Alessandra

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Intra-host evolution of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) has been shown by viral RNA analysis in subjects who naturally suppress plasma viremia to low levels, known as controllers. However, little is known about the variability of proviral DNA and the inter-relationships among contained systemic viremia, rate of reservoir reseeding and specific major histocompatibility complex (MHC) genotypes, in controllers. Here, we analysed the proviral DNA quasispecies of the env V1-V2 region, in PBMCs and in anatomical compartments of 13 long-term controller monkeys after 3.2 years of infection with simian/human immunodeficiency virus (SHIV)SF162P4cy. A considerable variation in the genetic diversity of proviral quasispecies was present among animals. Seven monkeys exhibited env V1-V2 proviral populations composed of both clusters of identical ancestral sequences and new variants, whereas the other six monkeys displayed relatively high env V1-V2 genetic diversity with a large proportion of diverse novel sequences. Our results demonstrate that in SHIVSF162P4cy-infected monkeys there exists a disparate pattern of intra-host viral diversity and that reseeding of the proviral reservoir occurs in some animals. Moreover, even though no particular association has been observed between MHC haplotypes and the long-term control of infection, a remarkably similar pattern of intra-host viral diversity and divergence was found within animals carrying the M3 haplotype. This suggests that in animals bearing the same MHC haplotype and infected with the same virus, viral diversity follows a similar pattern with similar outcomes and control of infection.

AB - Intra-host evolution of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) has been shown by viral RNA analysis in subjects who naturally suppress plasma viremia to low levels, known as controllers. However, little is known about the variability of proviral DNA and the inter-relationships among contained systemic viremia, rate of reservoir reseeding and specific major histocompatibility complex (MHC) genotypes, in controllers. Here, we analysed the proviral DNA quasispecies of the env V1-V2 region, in PBMCs and in anatomical compartments of 13 long-term controller monkeys after 3.2 years of infection with simian/human immunodeficiency virus (SHIV)SF162P4cy. A considerable variation in the genetic diversity of proviral quasispecies was present among animals. Seven monkeys exhibited env V1-V2 proviral populations composed of both clusters of identical ancestral sequences and new variants, whereas the other six monkeys displayed relatively high env V1-V2 genetic diversity with a large proportion of diverse novel sequences. Our results demonstrate that in SHIVSF162P4cy-infected monkeys there exists a disparate pattern of intra-host viral diversity and that reseeding of the proviral reservoir occurs in some animals. Moreover, even though no particular association has been observed between MHC haplotypes and the long-term control of infection, a remarkably similar pattern of intra-host viral diversity and divergence was found within animals carrying the M3 haplotype. This suggests that in animals bearing the same MHC haplotype and infected with the same virus, viral diversity follows a similar pattern with similar outcomes and control of infection.

KW - Diversity

KW - Evolution

KW - MCM

KW - MHC

KW - SHIV

KW - Viremic controllers

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