We recently reported an unconventional mechanism by which miRNAs inhibit HIV-1 
viral production. This occurs when miRNAs bind nonspecifically to the viral 
structural protein Gag, interfering with viral RNA-mediated Gag assembly at the 
plasma membrane. Consequently, misassembled viral complexes are redirected into 
the endocytic pathway where they are delivered to lysosomes for degradation. In 
this study, we demonstrate that autophagy is a critical mediator of the viral 
degradation pathway and that this pathway is not HIV-1 specific. Misassembled 
viral complexes were found to colocalize extensively with LC3 and p62 in late 
endosomes/lysosomes, demonstrating a convergence of autophagy with functional 
degradative compartments. Knocking down autophagosome formation machineries 
reduced this convergence, while treatment with autophagy-inducer rapamycin 
enhanced the convergence. Furthermore, similar autophagy-dependent nonspecific 
miRNA inhibition of murine leukemia virus (MLV) assembly was shown. Overall, 
these results reveal autophagy as a crucial regulator of the retroviral 
degradation pathway in host cells initiated by nonspecific miRNA-Gag 
interactions. These findings could have significant implications for 
understanding how cells may regulate retroviral complex assembly by miRNA 
expression and autophagy, and raise the possibility that similar regulations can 
occur in other biological contexts.