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Archives of Virology
Published in: Archives of Virology 9/2014

01-09-2014 | Original Article

Sequence heterogeneity in human immunodeficiency virus type 1 nef in patients presenting with rapid progression and delayed progression to AIDS

Authors: Poonam Gupta, Mohammad Husain, Charoo Hans, Hanu Ram, Supriya Singh Verma, Mohammad Misbah, L. S. Chauhan, Arvind Rai

Published in: Archives of Virology | Issue 9/2014

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Abstract

Genetic heterogeneity in the nef genes from human immunodeficiency virus type 1 (HIV-1)-infected rapid progressors (RPs) and long-term nonprogressors (LTNPs) was analyzed to identify various amino acid substitutions responsible for the discernible difference in disease progression. It was found that the majority of the strains characterized belonged to subtype C, followed by several BC recombinants and subtype A1. Complete nef subtype C sequences from 33 RPs and seven LTNPs were compared, and it was observed that, in the majority of the sequences from both groups, highly conserved functional motifs showed subtle changes. However, drastic changes were observed in two isolates from LTNPs where the arginine cluster was deleted, while in one of them, additionally, acidic residues were replaced by basic residues (EEEEE → RK(R)KKE). The deletion of the arginine cluster and the mutation of acidic residues to basic residues are predicted to delay disease development by abolishing CD4 downmodulation and causing diminution of major histocompatibility complex class I (MHC-I) downregulation, respectively. Nonetheless, this is an exclusive finding in these LTNPs, which necessitates their analysis at the functional level. The synonymous-to-nonsynonymous substitution ratio was greater than one in both of the groups, suggesting amino acid sequence conservation and functional robustness. Interpatient nucleotide distance within the group and between the two groups showed very little variation, confirming genetic relatedness among isolates.
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Metadata
Title
Sequence heterogeneity in human immunodeficiency virus type 1 nef in patients presenting with rapid progression and delayed progression to AIDS
Authors
Poonam Gupta
Mohammad Husain
Charoo Hans
Hanu Ram
Supriya Singh Verma
Mohammad Misbah
L. S. Chauhan
Arvind Rai
Publication date
01-09-2014
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 9/2014
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-014-2026-2

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