Investigating the mechanisms for persistence of HIV in human alveolar macrophages. (360G-Wellcome-105831_Z_14_Z)

The host antiviral immune response is relatively effective at recognising and eliminating most HIV-infected cells. However, HIV manipulates resting memory CD4 T cells and persistently resides in them in a latent state, resulting in formation of viral reservoirs. These reservoirs are poorly recognised by antiviral cytotoxic cells and are less susceptible to the effects of the current antiretroviral therapy (ART), leading to incomplete clearance of the infection. In the lung, alveolar macrophages (AM) have a long life span, can harbour HIV and are relatively resistant to the cytopathic effects of HIV, making them an important potential viral reservoir. Recently, we have shown that HIV persists in AM in HIV-infected individuals on long term ART despite undetectable plasma viraemia. This fellowship proposes using bronchoalveolar lavage (BAL) and peripheral blood obtained from HIV-infected and uninfected Malawian adults to address the hypothesis that HIVs ability to hinder immune recognitio n and block the induction of apoptosis leads to its persistence in AM. Specifically, the following questions will be addressed a) How does HIV hinder immune recognition of HIV-infected AM by cytotoxic cells? b) How does HIV block progression to apoptosis in HIV-infected AM? c) Which viral proteins are responsible for modulation of macrophages?