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LiteratureArticle Details
PMID: 18490657
Published · ppublish
English
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection.
Proceedings of the National Academy of Sciences of the United States of America
·Vol. 105
·No. 21
·2008-05-27
·Pages 7552-7
Abstract
The precise identification of the HIV-1 envelope glycoprotein (Env) responsible for productive clinical infection could be instrumental in elucidating the molecular basis of HIV-1 transmission and in designing effective vaccines. Here, we developed a mathematical model of random viral evolution and, together with phylogenetic tree construction, used it to analyze 3,449 complete env sequences derived by single genome amplification from 102 subjects with acute HIV-1 (clade B) infection. Viral env genes evolving from individual transmitted or founder viruses generally exhibited a Poisson distribution of mutations and star-like phylogeny, which coalesced to an inferred consensus sequence at or near the estimated time of virus transmission. Overall, 78 of 102 subjects had evidence of productive clinical infection by a single virus, and 24 others had evidence of productive clinical infection by a minimum of two to five viruses. Phenotypic analysis of transmitted or early founder Envs revealed a consistent pattern of CCR5 dependence, masking of coreceptor binding regions, and equivalent or modestly enhanced resistance to the fusion inhibitor T1249 and broadly neutralizing antibodies compared with Envs from chronically infected subjects. Low multiplicity infection and limited viral evolution preceding peak viremia suggest a finite window of potential vulnerability of HIV-1 to vaccine-elicited immune responses, although phenotypic properties of transmitted Envs pose a formidable defense.
MeSH Terms
AIDS Vaccines/immunology
Base Sequence
Disease Transmission, Infectious
Evolution, Molecular
Genetic Variation
HIV Antibodies/immunology
HIV Infections/immunology,transmission,virology
HIV-1/genetics,isolation & purification,physiology
Humans
Models, Biological
Molecular Sequence Data
Mutation
Phylogeny
RNA, Viral/blood,genetics
Receptors, CCR5/metabolism
Sequence Analysis, RNA
env Gene Products, Human Immunodeficiency Virus/genetics,immunology
Chemicals
AIDS Vaccines
HIV Antibodies
RNA, Viral
Receptors, CCR5
env Gene Products, Human Immunodeficiency Virus
References (32)
32 references, click to expand
-
Multiple V1/V2 env variants are frequently present during primary infection with human immunodeficiency virus type 1.J Virol. 2004 Oct;78(20):11208-18 PMID: 15452240
-
Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda.J Infect Dis. 2005 May 1;191(9):1403-9 PMID: 15809897
-
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.Nature. 1995 Jan 12;373(6510):123-6 PMID: 7816094
-
Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection.Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18514-9 PMID: 16339909
-
Inhibiting sexual transmission of HIV-1 infection.Nat Rev Microbiol. 2003 Oct;1(1):25-34 PMID: 15040177
-
Virus population homogenization following acute human immunodeficiency virus type 1 infection.J Virol. 2002 Dec;76(23):11953-9 PMID: 12414937
-
DNA recombination during PCR.Nucleic Acids Res. 1990 Apr 11;18(7):1687-91 PMID: 2186361
-
Selective transmission of CCR5-utilizing HIV-1: the 'gatekeeper' problem resolved?Nat Rev Microbiol. 2006 Apr;4(4):312-7 PMID: 16541138
-
HIV quasispecies and resampling.Science. 1996 Jul 26;273(5274):415-6 PMID: 8677432
-
Diversity in virus populations from genital secretions and peripheral blood from women recently infected with human immunodeficiency virus type 1.J Virol. 1995 Dec;69(12):8118-22 PMID: 7494333
-
Human immunodeficiency virus type 1 (HIV-1) diversity at time of infection is not restricted to certain risk groups or specific HIV-1 subtypes.J Virol. 2004 Jul;78(13):7279-83 PMID: 15194805
-
Virus isolates during acute and chronic human immunodeficiency virus type 1 infection show distinct patterns of sensitivity to entry inhibitors.J Virol. 2005 Jul;79(13):8454-69 PMID: 15956589
-
Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1.Immunity. 2007 Feb;26(2):257-70 PMID: 17306567
-
Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase.J Virol. 1995 Aug;69(8):5087-94 PMID: 7541846
-
HIV-1 genomic RNA diversification following sexual and parenteral virus transmission.Virology. 1992 Jul;189(1):103-10 PMID: 1376536
-
Incidence of HIV-1 dual infection and its association with increased viral load set point in a cohort of HIV-1 subtype C-infected female sex workers.J Infect Dis. 2004 Oct 1;190(7):1355-9 PMID: 15346349
-
Envelope-constrained neutralization-sensitive HIV-1 after heterosexual transmission.Science. 2004 Mar 26;303(5666):2019-22 PMID: 15044802
-
Gender differences in HIV-1 diversity at time of infection.Nat Med. 2000 Jan;6(1):71-5 PMID: 10613827
-
Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection.AIDS. 2003 Sep 5;17(13):1871-9 PMID: 12960819
-
Deciphering human immunodeficiency virus type 1 transmission and early envelope diversification by single-genome amplification and sequencing.J Virol. 2008 Apr;82(8):3952-70 PMID: 18256145
-
Modeling plasma virus concentration during primary HIV infection.J Theor Biol. 2000 Apr 7;203(3):285-301 PMID: 10716909
-
Viral dynamics in human immunodeficiency virus type 1 infection.Nature. 1995 Jan 12;373(6510):117-22 PMID: 7529365
-
Multiple, linked human immunodeficiency virus type 1 drug resistance mutations in treatment-experienced patients are missed by standard genotype analysis.J Clin Microbiol. 2005 Jan;43(1):406-13 PMID: 15635002
-
Natural variation in Vif: differential impact on APOBEC3G/3F and a potential role in HIV-1 diversification.PLoS Pathog. 2005 Sep;1(1):e6 PMID: 16201018
-
Antibody neutralization and escape by HIV-1.Nature. 2003 Mar 20;422(6929):307-12 PMID: 12646921
-
Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies.J Virol. 2005 Aug;79(16):10108-25 PMID: 16051804
-
Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1.J Virol. 1990 Dec;64(12):5840-50 PMID: 2243378
-
A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo.J Virol. 2003 Apr;77(8):5037-8 PMID: 12663814
-
Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants.Science. 1992 Feb 28;255(5048):1134-7 PMID: 1546316
-
Genotypic and phenotypic characterization of HIV-1 patients with primary infection.Science. 1993 Aug 27;261(5125):1179-81 PMID: 8356453
-
Pairwise comparisons of mitochondrial DNA sequences in stable and exponentially growing populations.Genetics. 1991 Oct;129(2):555-62 PMID: 1743491
-
Pervasive genomic recombination of HIV-1 in vivo.Genetics. 2004 Aug;167(4):1573-83 PMID: 15342499
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
Published
2008-05-27
Epub
2008-00-19
Pages
7552-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2387184
Subset
IM
Grants
NIAID NIH HHS · U01 AI067854 · United States
NIAID NIH HHS · AI41530 · United States
NIAID NIH HHS · AI67854 · United States
NIAID NIH HHS · U01 AI041530 · United States
NIAID NIH HHS · AI64518 · United States
NIAID NIH HHS · U19 AI067854 · United States
NIAID NIH HHS · P30 AI064518 · United States
NIAID NIH HHS · AI27767 · United States
NIAID NIH HHS · AI50410 · United States
NIAID NIH HHS · P30 AI050410 · United States
NIAID NIH HHS · P30 AI027767 · United States
NIAID NIH HHS · T32 AI007392 · United States
NIAID NIH HHS · AI61734 · United States
NIAID NIH HHS · P01 AI061734 · United States
Databases
GENBANK
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