Browsing by Author "Ping, Li-Hua."

Now showing 1 - 3 of 3

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.
(American Society for Microbiology., 2013) Ping, Li-Hua.; Joseph, Sarah B.; Anderson, Jeffrey A.; Abrahams, Melissa-Rose.; Salazar-Gonzalez, Jesus F.; Kincer, Laura P.; Treurnicht, Florette K.; Arney, Leslie.; Ojeda, Suany.; Zhang, Ming.; Keys, Jessica.; Potter, E. Lake.; Chu, Haitao.; Moore, Penelope L.; Salazar-Gonzalez, Maria.; Iyer, Shilpa.; Jabara, Cassandra.; Kirchherr, Jennifer.; Mapanje, Clement.; Ngandu, Nobubelo K.; Seoighe, Cathal.; Hoffman, Irving F.; Gao, Feng.; Tang, Yuyang.; Labranche, Celia.; Lee, Benhur.; Saville, Andrew.; Vermeulen, Marion.; Fiscus, Susan A.; Morris, Lynn.; Abdool Karim, Salim Safurdeen.; Haynes, Barton F.; Shaw, George M.; Korber, Bette T. M.; Hahn, Beatrice H.; Cohen, Myron S.; Montefiori, David Charles.; Williamson, Carolyn.; Swanstrom, Ronald.
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 under-glycosylated 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.
Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape.
(Nature Publishing Group., 2012) Moore, Penelope L.; Gray, Elin Solomonovna.; Wibmer, Constantinos Kurt.; Bhiman, Jinal N.; Nonyane, Molati.; Hermanus, Tandile.; Sheward, Daniel J.; Bajimaya, Shringkhala.; Abrahams, Melissa-Rose.; Tumba, Nancy Lola.; Ping, Li-Hua.; Ngandu, Nobubelo K.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Swanstrom, Ronald.; Seaman, Michael S.; Williamson, Carolyn.; Morris, Lynn.;
Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1–infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.
Vertical T cell immunodominance and epitope entropy determine HIV-1 escape.
(American Society for Clinical Investigation., 2012) Liu, Michael K. P.; Hawkins, Natalie.; Ritchie, Adam J.; Ganusov, Vitaly.; Whale, Victoria.; Brackenridge, Simon.; Li, Hui.; Pavlicek, Jeffrey W.; Cai, Fangping.; Abrahams, Melissa-Rose.; Treurnicht, Florette K.; Hraber, Peter.; Riou, Catherine.; Gray, Clive M.; Ferrari, Guido.; Tanner, Rachel.; Ping, Li-Hua.; Anderson, Jeffrey A.; Swanstrom, Ronald.; Cohen, Myron S.; Abdool Karim, Salim Safurdeen.; Haynes, Barton F.; Borrow, Persephone.; Perelson, Alan S.; Shaw, George M.; Hahn, Beatrice H.; Williamson, Carolyn.; Korber, Bette T. M.; Gao, Feng.; Self, Steven G.; McMichael, Andrew.; Goonetilleke, Nilu.
HIV-1 accumulates mutations in and around reactive epitopes to escape recognition and killing by CD8+ T cells. Measurements of HIV-1 time to escape should therefore provide information on which parameters are most important for T cell–mediated in vivo control of HIV-1. Primary HIV-1–specific T cell responses were fully mapped in 17 individuals, and the time to virus escape, which ranged from days to years, was measured for each epitope. While higher magnitude of an individual T cell response was associated with more rapid escape, the most significant T cell measure was its relative immunodominance measured in acute infection. This identified subject-level or “vertical” immunodominance as the primary determinant of in vivo CD8+ T cell pressure in HIV-1 infection. Conversely, escape was slowed significantly by lower population variability, or entropy, of the epitope targeted. Immunodominance and epitope entropy combined to explain half of all the variability in time to escape. These data explain how CD8+ T cells can exert significant and sustained HIV-1 pressure even when escape is very slow and that within an individual, the impacts of other T cell factors on HIV-1 escape should be considered in the context of immunodominance.