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Browsing by Author "Carlson, Jonathan M."

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    Brief report: selection of HIV-1 variants with higher transmission potential by 1% tenofovir gel microbicide.
    (Wolters Kluwer Health., 2017) Ngandu, Nobubelo K.; Carlson, Jonathan M.; Chopera, Denis Rutendo.; Ndabambi, Nonkululeko.; Abdool Karim, Quarraisha.; Abdool Karim, Salim Safurdeen.; Williamson, Carolyn.
    Abstract available in pdf.
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    Intersubtype differences in the effect of a rare p24 Gag mutation on HIV-1 replicative fitness.
    (American Society for Microbiology., 2012) Chopera, Denis Rutendo.; Cotton, Laura A.; Zawaira, Alexander.; Mann, Jaclyn Kelly.; Ngandu, Nobubelo K.; Ntale, Roman.; Carlson, Jonathan M.; Mlisana, Koleka Patience.; Woodman, Zenda.; de Assis Rosa, Debra.; Martin, Eric.; Miura, Toshiyuki.; Pereyra, Florencia.; Walker, Bruce D.; Gray, Clive M.; Martin, Darren Patrick.; Ndung'u, Peter Thumbi.; Brockman, Mark A.; Abdool Karim, Salim Safurdeen.; Brumme, Zabrina L.; Williamson, Carolyn.
    Certain immune-driven mutations in HIV-1, such as those arising in p24Gag, decrease viral replicative capacity. However, the intersubtype differences in the replicative consequences of such mutations have not been explored. In HIV-1 subtype B, the p24Gag M250I mutation is a rare variant (0.6%) that is enriched among elite controllers (7.2%) (P 0.0005) and appears to be a rare escape variant selected by HLA-B58 supertype alleles (P<0.01). In contrast, in subtype C, it is a relatively common minor polymorphic variant (10 to 15%) whose appearance is not associated with a particular HLA allele. Using site-directed mutant viruses, we demonstrate that M250I reduces in vitro viral replicative capacity in both subtype B and subtype C sequences. However, whereas in subtype C downstream compensatory mutations at p24Gag codons 252 and 260 reduce the adverse effects of M250I, fitness costs in subtype B appear difficult to restore. Indeed, patient-derived subtype B sequences harboring M250I exhibited in vitro replicative defects, while those from subtype C did not. The structural implications of M250I were predicted by protein modeling to be greater in subtype B versus C, providing a potential explanation for its lower frequency and enhanced replicative defects in subtype B. In addition to accounting for genetic differences between HIV-1 subtypes, the design of cytotoxic-T-lymphocyte-based vaccines may need to account for differential effects of host-driven viral evolution on viral fitness.
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    Nef-mediated down-regulation of CD4 and HLA class I in HIV-1 subtype C infection: association with disease progression and influence of immune pressure.
    (Elsevier., 2014) Mann, Jaclyn Kelly.; Chopera, Denis Rutendo.; Omarjee, Saleha.; Kuang, Xiaomei T.; Le, Anh Q.; Anmole, Gursev.; Danroth, Ryan.; Mwimanzi, Philip.; Reddy, Tarylee.; Carlson, Jonathan M.; Radebe, Mopo.; Goulder, Philip Jeremy Renshaw.; Walker, Bruce D.; Abdool Karim, Salim Safurdeen.; Novitsky, Vladimir.; Williamson, Carolyn.; Brockman, Mark A.; Brumme, Zabrina L.; Ndung'u, Peter Thumbi.
    Abstract available in pdf.