Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection

Louis Alexander, Emma Weiskopf, Thomas C. Greenough, Nathan C. Gaddis, Marcy R. Auerbach, Michael H. Malim, Stephen J. O'Brien, Bruce D. Walker, John L. Sullivan, Ronald Charles Desrosiers

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Factors accounting for long-term nonprogression may include infection with an attenuated strain of human immunodeficiency virus type 1 (HIV-1), genetic polymorphisms in the host, and virus-specific immune responses. In this study, we examined eight individuals with nonprogressing or slowly progressing HIV-1 infection, none of whom were homozygous for host-specific polymorphisms (CCR5-Δ32, CCR2-64I, and SDF-1-3'A) which have been associated with slower disease progression. HIV-1 was recovered from seven of the eight, and recovered virus was used for sequencing the full-length HIV-1 genome; full-length HIV-1 genome sequences from the eighth were determined following amplification of viral sequences directly from peripheral blood mononuclear cells (PBMC). Longitudinal studies of one individual with HIV-1 that consistently exhibited a slow/low growth phenotype revealed a single amino acid deletion in a conserved region of the gp41 transmembrane protein that was not seen in any of 131 envelope sequences in the Los Alamos HIV-1 sequence database. Genetic analysis also revealed that five of the eight individuals harbored HIV-1 with unusual 1- or 2-amino-acid deletions in the Gag sequence compared to subgroup B Gag consensus sequences. These deletions in Gag have either never been observed previously or are extremely rare in the database. Three individuals had deletions in Nef, and one had a 4-amino- acid insertion in Vpu. The unusual polymorphisms in Gag, Env, and Nef described here were also found in stored PBMC samples taken 3 to 11 years prior to, or in one case 4 years subsequent to, the time of sampling for the original sequencing. In all, seven of the eight individuals exhibited one or more unusual polymorphisms; a total of 13 unusual polymorphisms were documented in these seven individuals. These polymorphisms may have been present from the time of initial infection or may have appeared in response to immune surveillance or other selective pressures. Our results indicate that unusual, difficult-to-revert polymorphisms in HIV-1 can be found associated with slow progression or nonprogression in a majority of such cases.

Original languageEnglish (US)
Pages (from-to)4361-4376
Number of pages16
JournalJournal of Virology
Volume74
Issue number9
DOIs
StatePublished - 2000
Externally publishedYes

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Human immunodeficiency virus 1
HIV-1
genetic polymorphism
Infection
infection
amino acid deletion
mononuclear leukocytes
Amino Acids
Blood Cells
Genome
Databases
Viruses
viruses
transmembrane proteins
genome
consensus sequence
Consensus Sequence
Genetic Polymorphisms
Virus Diseases
longitudinal studies

ASJC Scopus subject areas

  • Immunology

Cite this

Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection. / Alexander, Louis; Weiskopf, Emma; Greenough, Thomas C.; Gaddis, Nathan C.; Auerbach, Marcy R.; Malim, Michael H.; O'Brien, Stephen J.; Walker, Bruce D.; Sullivan, John L.; Desrosiers, Ronald Charles.

In: Journal of Virology, Vol. 74, No. 9, 2000, p. 4361-4376.

Research output: Contribution to journalArticle

Alexander, L, Weiskopf, E, Greenough, TC, Gaddis, NC, Auerbach, MR, Malim, MH, O'Brien, SJ, Walker, BD, Sullivan, JL & Desrosiers, RC 2000, 'Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection', Journal of Virology, vol. 74, no. 9, pp. 4361-4376. https://doi.org/10.1128/JVI.74.9.4361-4376.2000
Alexander, Louis ; Weiskopf, Emma ; Greenough, Thomas C. ; Gaddis, Nathan C. ; Auerbach, Marcy R. ; Malim, Michael H. ; O'Brien, Stephen J. ; Walker, Bruce D. ; Sullivan, John L. ; Desrosiers, Ronald Charles. / Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection. In: Journal of Virology. 2000 ; Vol. 74, No. 9. pp. 4361-4376.
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