Browsing by Author "Bhattacharya, Tanmoy"

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    HIV evolution in early infection: selection pressures, patterns of insertion and deletion, and the impact of APOBEC
    (Public Library of Science, 2009) Wood, Natasha; Bhattacharya, Tanmoy; Keele, Brandon F; Giorgi, Elena; Liu, Michael; Gaschen, Brian; Daniels, Marcus; Ferrari, Guido; Haynes, Barton F; McMichael, Andrew
    Author Summary HIV is a rapidly evolving virus, displaying enormous genetic diversity between and even within infected individuals, with implications for vaccine design and drug treatment. Yet, recent research has shown that most new infections result from transmission of a single virus resulting in a homogeneous viral population in early infection. The process of diversification from the transmitted virus provides information about the selection pressures experienced by the virus during the establishment of a new infection. In this paper, we studied early diversification of the envelope gene in a cohort of 81 subjects acutely infected with HIV-1 subtype B and found evidence of adaptive evolution, with a proportion of sites that tended to diversify more rapidly than expected under a model of neutral evolution. Several of these rapidly diversifying sites facilitate escape from early cytotoxic immune responses. Interestingly, hypermutation of the virus, brought about by host proteins as a strategy to restrict infection, appeared to be associated with early immune escape. In addition to single base substitutions, insertions and deletions are an important aspect of HIV evolution. We show that insertion and deletion mutations occur evenly across the gene, but are preferentially fixed in the variable loop regions.
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    Optimal combinations of broadly neutralizing antibodies for prevention and treatment of HIV-1 Clade C infection
    (Public Library of Science, 2016) Wagh, Kshitij; Bhattacharya, Tanmoy; Williamson, Carolyn; Robles, Alex; Bayne, Madeleine; Garrity, Jetta; Rist, Michael; Rademeyer, Cecilia; Yoon, Hyejin; Lapedes, Alan; Gao, Hongmei; Greene, Kelli; Louder, Mark K; Kong, Rui; Karim, Salim Abdool; Burton, Dennis R; Barouch, Dan H; Nussenzweig, Michel C; Mascola, John R; Morris, Lynn; Montefiori, David C; Korber, Bette; Seaman, Michael S
    Author Summary In recent years, a new generation of monoclonal antibodies has been isolated from HIV-1 infected individuals that exhibit broad and potent neutralizing activity when tested against diverse strains of virus. There is a high level of interest in the field in determining if these antibodies can be used to prevent or treat HIV-1 infection. Because HIV-1 is adept at escaping from immune recognition, it is generally thought that combinations of multiple antibodies targeting different sites will be required for efficacy, much the same as seen for conventional antiretroviral drugs. How many and which antibodies to include in such combinations is not known. In this study, a new mathematical model was developed and used to accurately predict various measures of neutralizing activity for all possible combinations having a total of 2, 3, or 4 of the most promising antibodies. Through a systematic and comprehensive comparison, we identified optimal combinations of antibodies that best complement one another for enhanced anti-viral activity, and therefore may be most effective for the prevention or treatment of HIV-1 infection. These results provide important parameters that inform the selection of antibodies to develop for clinical use.