Persistence of primary patient-derived HIV-1 strains in myeloid cells and modes of virus transmission to T cells: Susceptibility to bNAbs and role of MIF/CD74 axis.

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The recent developments in the field of broadly neutralizing antibodies (bNAbs) against HIV-1 open avenues for antiretroviral therapy and inspire hope for a potential vaccine, either prophylactic or therapeutic. However, several important issues remain unclear. For instance, it has been shown that some primary HIV-1 strains infecting myeloid cells are relative refractory against neutralization by bnAbs, raising the question whether bNAbs allow attacking this important HIV-1 reservoir and whether modes of primary HIV-1 strain persistence in these cells differ from that of lab-adapted strains.We hypothesize that primary in South America circulating BF-recombinant strains, as well as transmitted/founder (T/F) HIV-1 strains efficiently persist within myeloid cells and might thereby escape from the activity of bNAbs when transmitted from cell-to-cell. Mechanistically, we postulate that primary HIV-1 strains efficiently induce myeloid-cell internal virus-containing-compartments (VCCs) that are shielded from access by bNAbs. Furthermore, we postulate that manipulation of the CD74-MIF axis by this primary HIV-1 strains is a strategy to enhance the efficiency of cell-to-cell transmission and viral spread. This project will reveal modes of primary HIV-1 persistence and transmission and furthermore give prospects to evaluate bNAbs as potent inhibitors of pertinent viral transmission routes using relevant viral strains.