Fellowship

Characterisation of HIV-1 Env in virus reservoirs found in lymph nodes and peripheral blood

Despite the fact that antiretroviral therapy (ART) has significantly increased the lifespan of HIV-infected people and improved their quality of living, it is not curative due to the presence of a latent reservoir. Latency is described as the incorporation of intact replication-competent viruses into the genome of the host cell with no virus production. Since the viral envelope is responsible for attaching to the target cell, we aim to determine the characteristics of the envelope that allows them to persist within compartments such as the lymph node and peripheral blood mononuclear cells (PBMCs). By using techniques such as polymerase chain reaction (PCR), cloning, sequencing, infectivity and neutralisation assays, as well as cell-cell spread assays, Govindsamy and her team will amplify, clone, and sequence envelope. Furthermore they will determine from the sequences, if there are patient-specific mutations in envelope and if so, they will be able to determine which characteristics enable the virus to persist within these reservoirs. The downstream assays will enable them to determine if these envelopes are able to infect and whether the broadly neutralising antibodies can neutralise the viruses that contain these envelopes. Lastly, by executing the cell-cell spread assay, they will determine the ability of envelope to make the spread of the virus possible within the circulation in comparison to tissues. By studying these attributes, Govindsamy’s project could inform cure strategies.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.