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PMID: 8995651 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Investigation of the dynamics of the spread of human immunodeficiency virus to brain and other tissues by evolutionary analysis of sequences from the p17gag and env genes.

Journal of virology ·Vol. 71 ·No. 2 ·1997-02-00 ·Pages 1272-80

Hughes ES, Bell JE, Simmonds P

Abstract

The time of spread of human immunodeficiency virus type 1 (HIV-1) from lymphoid to nonlymphoid tissues in the course of infection was investigated by sequence comparisons of variants infecting a range of lymphoid and nonlymphoid tissues from three individuals with AIDS in the pl7gag gene and regions flanking the V1/V2 hypervariable regions. Phylogenetic analysis in both regions revealed several lineages in each individual that contained sequences from both lymphoid and nonlymphoid tissues such as the brain. This observation contrasts strongly with the previously described organ-specific sequences in the V3 region in this study population and other investigations. Although individual pairwise comparisons of relatively short sequences such as p17gag are subject to considerable stochastic error, we found that the diversity of gag sequences in variants from lymphoid tissue was consistently lower than that found among variants amplified from the brain. By estimating mean synonymous pairwise distances in the p17gag region, we were able to make an approximate calculation of the ages of populations in different tissues. Those from lymphoid tissue ranged from 2.65 to 5.6 years in the three study subjects, compared with 4.1 to 6.2 years for variants in the brain. Indeed, variants infecting the brain were no more closely related to each other than they were to variants infecting other tissues in the body. In two of the three individuals, these times of divergence indicate that infection of the brain may have occurred as an early event in the progression to disease, preceding the onset of AIDS by several years. This study is the first in which it was possible to estimate times of diversification in different tissues in vivo and is of importance in understanding the dynamics of the spread of HIV-1 into nonlymphoid tissues and its possible adaptation for replication in different cell types.

MeSH Terms
Acquired Immunodeficiency Syndrome/virology Brain/virology Evolution, Molecular Genes, Viral Genes, env Genes, gag HIV-1/genetics Humans Molecular Sequence Data Phylogeny Sequence Analysis
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hughes E S
Department of Medical Microbiology, University of Edinburgh, United Kingdom.
Bell J E
Simmonds P
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44 references, click to expand
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.71.2.1272-1280.1997
Published
1997-02-00
Pages
1272-80
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC191182
Subset
IM
Databases
GENBANK
U79785, U79786, U79787, U79788, U79789, U79790, U79791, U79792, U79793, U79794, U79795, U79796, U79797, U79798, U79799, U79800, U79801, U79802, U79803, U79804, U79805, U79806, U79807, U79808, U79809, U79810, U79811, U79812, U79813, U79814
External Links
PubMed source DOI: 10.1128/JVI.71.2.1272-1280.1997 PMC Full Text View journal details
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