Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection
Authors
Alexander, LouisWeiskopf, Emma
Greenough, Thomas C.
Gaddis, Nathan C.
Auerbach, Marcy R.
Malim, Malcolm H.
O'Brien, Stephen J.
Walker, Bruce D.
Sullivan, John L.
Desrosiers, Ronald C.
Document Type
Journal ArticlePublication Date
2000-05-01Keywords
Amino Acid SequenceAnimals
Cells, Cultured
Chemokine CXCL12
Chemokines, CXC
Disease Progression
Gene Products, gag
Gene Products, nef
Gene Products, vpr
Genotype
HIV Infections
HIV-1
HLA Antigens
Haplotypes
Humans
Macaca mulatta
Molecular Sequence Data
*Polymorphism, Genetic
Receptors, CCR2
Receptors, CCR5
*Receptors, Chemokine
Receptors, Cytokine
Sequence Homology, Amino Acid
Simian immunodeficiency virus
gag Gene Products, Human Immunodeficiency Virus
nef Gene Products, Human Immunodeficiency Virus
vpr Gene Products, Human Immunodeficiency Virus
Immunology and Infectious Disease
Pediatrics
Metadata
Show full item recordAbstract
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-Delta32, 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.Source
J Virol. 2000 May;74(9):4361-76. Link to article on publisher's websitePermanent Link to this Item
http://hdl.handle.net/20.500.14038/43427PubMed ID
10756051Related Resources
Link to Article in PubMedCollections
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