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.
aNebraska Center for Virology and the School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
bDana-Farber Cancer Institute, USA
cHarvard Medical School, Boston, Massachusetts, USA
dRega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat, Leuven, Belgium.
* Current Address: Instituto Carlos Chagas-FIOCRUZ, Curitiba, Paraná, Brazil.
Received 30 March, 2009
Revised 2 June, 2009
Accepted 9 June, 2009
Correspondence to Dr Charles Wood, Nebraska Center for Virology, School of Biological Sciences, University of Nebraska-Lincoln, Morrison Center, P.O. Box 830666, Lincoln, NE 68583-0900, USA. Tel: +1 402 472 4550; fax: +1 402 472 3323; e-mail: email@example.com