Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2009 Sep 10;23(14):1817-28.
doi: 10.1097/QAD.0b013e32832f3da6.

A comparative study of HIV-1 clade C env evolution in a Zambian infant with an infected rhesus macaque during disease progression

For Yue Tso  1 , Federico G Hoffmann, Damien C Tully, Philippe Lemey, Robert A Rasmussen, Hong Zhang, Ruth M Ruprecht, Charles Wood
Affiliations
Comparative Study

A comparative study of HIV-1 clade C env evolution in a Zambian infant with an infected rhesus macaque during disease progression

For Yue Tso et al. AIDS. .

Abstract

Objective: To evaluate whether HIV-1 clade C (HIV-C) envelope variations that arise during disease progression in rhesus macaque model reflect changes that occur naturally in human infection.

Design: An infant macaque was infected with SHIV-1157i, an R5 tropic clade C SHIV, that expresses a primary HIV-C envelope derived from an infected human infant and monitored over a 5-year period. Genetic variation of the V1-V5 envelope region, which is the main target for humoral immune responses, derived from the infected macaque and infant was examined.

Methods: The V1-V5 envelope region was cloned and sequenced from longitudinal peripheral blood mononuclear cell samples collected from the infected macaque and infant. Phylogenetic analysis [phylogenetic tree, diversity, divergence, ratio of nonsynonymous (dN) and synonymous substitution (dS) and dN distribution] was performed. Plasma RNA viral load, CD4(+) T-cell count, changes in the length of V1-V5 region, putative N-linked glycosylation site number and distribution were also measured.

Results: Phylogenetic analysis revealed that changes in the macaque closely reflected those of the infant during disease progression. Similar distribution patterns of dN and hot spots were observed between the macaque and infant. Analysis of putative N-linked glycosylation sites revealed several common variations between the virus populations in the two host species. These variations correlate with decline of CD4 T-cell count in the macaque and might be linked with disease progression.

Conclusion: SHIV-C infection of macaque is a relevant animal model for studying variation of primary HIV-C envelope during disease progression and could be used to analyze the selection pressures that are associated with those changes.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
(A). Pvu I (P) was introduced into the 3′ half of SHIV-vpu+ (28) proviral DNA. The 2.0 Kb Kpn I - Pvu I fragment of HIV-1 1157i (spanning most of gp120 as well as the entire gp41 extracellular domain and the transmembrane region [TM]) was amplified to replace the corresponding region in the SHIV-vpu+ envelope. The modified 3′ half of SHIV-vpu+ was ligated with the 5′ half of SHIV-vpu+ proviral DNA to form the full length SHIV-1157i [28, 29]. (B) Plasma viral RNA load and (C) absolute CD4+ T-cell counts.
Fig. 2
Fig. 2
Consensus tree from a Neighbor-Joining bootstrap analysis showing phylogenetic relationships among viral samples derived from the longitudinal follow-up of the macaque (RPn-8, solid lines) and infant (1157i, dashed lines) in this study. Labels indicate the source and time of sample collection. For example, RPn-8 20M corresponds to viral sequences coming from the macaque, and collected 20 months post-inoculation. Cut-off value for the condensed tree was set at 75%.
Fig. 3
Fig. 3
Changes in (A) genetic diversity and (B) divergence over time for infant 1157i and macaque RPn-8. Genetic diversity is calculated from the average number of nucleotide differences within a given time point. Genetic divergence is calculated from the average number of changes between each time point and the initial population. (C) non-synonymous and synonymous (dN/dS) ratio over time for infant 1157i and macaque RPn-8. (D) Estimated number of observed non-synonymous substitutions per codon within V1-V5 region in infant 1157i and macaque RPn-8. Results represented are cumulative of all time points for human or macaque. M represents either months of age in human or months post inoculation in macaque. Numbers of the horizontal axis correspond to amino acid position within the sequence alignment. All variable loops and constant regions within the alignment are labeled.
Fig. 4
Fig. 4
(A) V1-V5 consensus sequence of infant 1157i at 0 month of age and inoculation strain SHIV-1157i is shown. Putative N-linked glycosylation sites (PNGSs) within sequences from all time points were located as described in Methods. n represents relatively conserved PNGSs in macaque or human over time. N represents variable PNGSs in macaque or human over time. Common variable PNGSs between macaque and human are circled. Variable regions and constant regions are shown along the bottom of the sequences. (B) sequence alignment of V4 in infant 1157i and macaque RPn-8 at different time points. Sequences were aligned using Bioedit 7.0.9.0. Sequences represented here are examples from each time points. These are not consensus sequences and do not represent all observed variations within V4.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gaschen B, Taylor J, Yusim K, Foley B, Gao F, Lang D, et al. Diversity considerations in HIV-1 vaccine selection. Science. 2002;296:2354–2360. - PubMed
    1. Geyer H, Holschbach C, Hunsmann G, Schneider J. Carbohydrates of human immunodeficiency virus. Structures of oligosaccharides linked to the envelope glycoprotein 120. J Biol Chem. 1988;263:11760–11767. - PubMed
    1. Sagar M, Wu X, Lee S, Overbaugh J. Human immunodeficiency virus type 1 V1-V2 envelope loop sequences expand and add glycosylation sites over the course of infection, and these modifications affect antibody neutralization sensitivity. J Virol. 2006;80:9586–9598. - PMC - PubMed
    1. Saunders CJ, McCaffrey RA, Zharkikh I, Kraft Z, Malenbaum SE, Burke B, et al. The V1, V2, and V3 regions of the human immunodeficiency virus type 1 envelope differentially affect the viral phenotype in an isolate-dependent manner. J Virol. 2005;79:9069–9080. - PMC - PubMed
    1. Stevceva L, Yoon V, Anastasiades D, Poznansky MC. Immune responses to HIV Gp120 that facilitate viral escape. Curr HIV Res. 2007;5:47–54. - PubMed

Publication types

MeSH terms

Substances