HIV-1 Hijacks HGF/c-MET Signaling to Promote Viral Entry and Replication in Primary CD4⁺ T Cells

Many cellular proteins contribute to HIV-1 replication and innate immunity. However, the role of c-MET during HIV-1 infection is unknown.

Here, we demonstrate that HIV-1 infection increases c-MET mRNA and phosphorylated MET protein (p-MET) levels in CD4+ T cells, and inhibition of HIV-1 replication reduces p-MET levels. Knockout (KO) of c-MET in MT4 cells reduced HIV-1 Gag mRNA and protein levels as well as viral capsid release into the supernatant, indicating that c-MET supports HIV-1 replication. Notably, cell surface expression of the CD4 receptor and CXCR4 coreceptor also decreased in c-MET KO cells, suggesting that c-MET facilitates HIV-1 replication by regulating viral entry.