139 HIV-2 capsids distinguishing high and low virus load patients in a West African community cohort

Onyango, C. et al. (2009) 139 HIV-2 capsids distinguishing high and low virus load patients in a West African community cohort. JAIDS: Journal of Acquired Immune Deficiency Syndromes, 51, (doi: 10.1097/01.qai.0000351096.55643.09)

Abstract

HIV-2 causes AIDS similar to HIV-1; however, most HIV-2 infected patients show no disease and have low plasma virus load (VL). A detailed sequence analysis of HIV-2 p26 capsid (P26) variation in a community cohort was undertaken with the primary objective of detecting p26 variation that correlated with virus load. Activities: Sensitive methods were developed to generate virus sequences from high and low virus load subjects, providing information from both healthy and progressing HIV-2+ patients. Results: Three amino acid polymorphisms in p26 were identified that correlated significantly with VL. Proline residues at the three sites (PPP) were found more frequently in lower VL subjects while p26 with non-proline residues at all three sites (non-PPP) were isolated more frequently from high VL subjects. Structural modeling of these capsid variants revealed an increase in capsid dimer binding energies associated with the high VL (non-PPP) variants. In vitro virus replication supported the conclusion that these residues influence TRIM5α interaction, with PPP variants having increased susceptibility to TRIM5α restriction. The cellular immune responses to HIV-2 antigens in PPP patients were significantly higher than in non-PPP patients, indicating that capsid phenotype may also influence antigen presentation. Lessons: These results demonstrate that HIV-2 replication in vivo can be linked to p26 variation and provide a new basis for understanding HIV-2 pathogenesis.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cotten, Professor Matthew
• Authors: Onyango, C., Leligdowicz, A., Yokoyama, M., Sato, H., Song, H., Nakayama, E., Shioda, T., Jaye, A., Whittle, H., Rowland-Jones, S., and Cotten, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: JAIDS: Journal of Acquired Immune Deficiency Syndromes
• Publisher: Lippincott, Williams & Wilkins
• ISSN: 1525-4135
• ISSN (Online): 1944-7884