Identification and Characterization of Positively Selected Mutations in Nef of Four HIV-1 Major Subtypes from Los Alamos National Laboratory

Background:Human immunodeficiency virus-1 (HIV-1) mutates rapidly to escape host immune pressure. This results in the generation of positively selected mutations (PSM) throughout the viral genome. Escape mutations in Nef, one of the accessory proteins of HIV-1, which plays an important role in viral pathogenicity have previously been identified in several large cohort studies, but the evolution of PSMs overtime in various HIV-1 subtypes remains unknown.Methods:161 clade A1, 3093 clade B, 647 clade C and 115 clade D HIV-1 nef sequences were obtained from the HIV Database of Los Alamos National Laboratory and aligned using MEGA 6.0. The sequences from each clade were grouped based on the year of collection. Quasi analysis was used to identify PSMs and the number and locations of PSMs were compared among different subtypes.Results:PSMs for all four subtypes were distributed across the sequence of Nef, and conserved residues F90, W113, PxxPxR (a.a 72-77) remain unaltered overtime. The frequency of PSMs was stable among subtype B sequences but increased overtime for other subtypes. Phylogenetic analysis shows that sequences containing PSMs tend to cluster together at both inter and intra- subtype levels.Conclusion:Identification of PSMs and their changes overtime within various subtypes of HIV-1 is important in defining global viral evolutionary patterns that can provide insights for designing therapeutic strategies.

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QUASI analysis of the HIV-1 envelope sequences in the Los Alamos National Laboratory HIV sequence database: pattern and distribution of positive selection sites and their frequencies over yearsThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process.

Biochemistry and Cell Biology ◽

10.1139/o06-143 ◽

2007 ◽

Vol 85 (2) ◽

pp. 259-264 ◽

Cited By ~ 4

Author(s):

Binhua Liang ◽

Ma Luo ◽

T. Blake Ball ◽

Francis A. Plummer

Keyword(s):

Positive Selection ◽

National Laboratory ◽

Sequence Database ◽

Alamos National Laboratory ◽

Los Alamos ◽

Los Alamos National Laboratory ◽

Central Target ◽

Conserved Regions ◽

Geographical Regions ◽

Hiv 1

The envelope (env) protein of human immunodeficiency virus type 1 (HIV-1) plays a crucial role in virus entry and is a central target for HIV vaccine design. Using the QUASI program, we analyzed the conserved regions of all currently available env sequences in the Los Alamos National Laboratory HIV Sequence Database and identified positive selection (PS) sites that are likely to be restricted by host immune responses. We found that PS sites are dispersed across conserved regions of env sequence, and that the C3, C4, and C5 regions were the most targeted. Several regions were identified as being PS free and were mainly distributed in the C1 and C2 regions. When comparing individual QUASI PS site frequencies across clades and geographical regions with the overall frequency of the entire env database, the env sequences from North America showed significantly lower PS site frequency, while those from Asia were significantly higher using Student's t test. The QUASI PS site frequency of env proteins from viruses isolated from different years showed that the PS site frequencies of the env population increased over time. Our study provides an overview of PS sites across the conserved regions of HIV-1 env sequences.

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