Comparison of viral Env proteins from acute and chronic infections with subtype C human immunodeficiency virus type 1 identifies differences in glycosylation and CCR5 utilization and suggests a new strategy for immunogen design.

Abstract

Understanding human immunodeficiency virus type 1 (HIV-1) transmission is central to developing effective prevention strategies, including a vaccine. We compared phenotypic and genetic variation in HIV-1 env genes from subjects in acute/early infection and subjects with chronic infections in the context of subtype C heterosexual transmission. We found that the transmitted viruses all used CCR5 and required high levels of CD4 to infect target cells, suggesting selection for replication in T cells and not macrophages after transmission. In addition, the transmitted viruses were more likely to use a maraviroc-sensitive conformation of CCR5, perhaps identifying a feature of the target T cell. We confirmed an earlier observation that the transmitted viruses were, on average, modestly underglycosylated relative to the viruses from chronically infected subjects. This difference was most pronounced in comparing the viruses in acutely infected men to those in chronically infected women. These features of the transmitted virus point to selective pressures during the transmission event. We did not observe a consistent difference either in heterologous neutralization sensitivity or in sensitivity to soluble CD4 between the two groups, suggesting similar conformations between viruses from acute and chronic infection. However, the presence or absence of glycosylation sites had differential effects on neutralization sensitivity for different antibodies. We suggest that the occasional absence of glycosylation sites encoded in the conserved regions of env, further reduced in transmitted viruses, could expose specific surface structures on the protein as antibody targets.

• Authors: Li-Hua Ping, Sarah B Joseph, Jeffrey A Anderson, Melissa-Rose Abrahams, Jesus F Salazar-Gonzalez, Laura P Kincer, Florette K Treurnicht, Leslie Arney, Suany Ojeda, Ming Zhang, Jessica Keys, E Lake Potter, Haitao Chu, Penny Moore, Maria G Salazar, Shilpa Iyer, Cassandra Jabara, Jennifer Kirchherr, Clement Mapanje, Nobubelo Ngandu, Cathal Seoighe, Irving Hoffman, Feng Gao, Yuyang Tang, Celia Labranche, Benhur Lee, Andrew Saville, Marion Vermeulen, Susan Fiscus, Lynn Morris, Salim Abdool Karim, Barton F Haynes, George M Shaw, Bette T Korber, Beatrice H Hahn, Myron S Cohen, David Montefiori, Carolyn Williamson, Ronald Swanstrom, CAPRISA Acute Infection Study and the Center for HIV-AIDS Vaccine Immunology Consortium
• Journal: Journal of virology (J Virol) Vol. 87 Issue 13 Pg. 7218-33 (Jul 2013) ISSN: 1098-5514 [Electronic] United States
• PMID: 23616655 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Receptors, CCR5
• Viral Envelope Proteins

Topics

• Base Sequence
• Cloning, Molecular
• Cluster Analysis
• Cohort Studies
• Female
• Genetic Variation
• Glycosylation
• HIV Infections (metabolism, prevention & control, transmission)
• HIV-1 (metabolism)
• Humans
• Malawi
• Male
• Molecular Sequence Data
• Neutralization Tests
• Phylogeny
• Protein Conformation
• Receptors, CCR5 (chemistry, metabolism)
• Sequence Alignment
• Sequence Analysis, DNA
• Sex Factors
• South Africa
• T-Lymphocytes (immunology, virology)
• Viral Envelope Proteins (genetics, metabolism)
• Virus Replication (physiology)