Cell proliferation is not required for productive HIV-1 infection of macrophages

Lentiviruses, including HIV-1, are considered a rare example of retroviruses which do not require cell proliferation for their replication. However, this notion was questioned in several publications where productive HIV-1 infection was found to be restricted to a small fraction of macrophages with proliferative capacity. Since the mode of HIV-1 replication in macrophages is of great clinical relevance, we performed a single-cell analysis of HIV-1 replication and [3H]thymidine incorporation. Our results indicate that while 17% macrophages were detected as HIV-1 DNA-positive 12 hr after infection, only 2% of those cells had incorporated tritium, about the same percentage as in the uninfected cell population. Forty-eight hours after infection, 38% macrophages were HIV-1 DNA-positive and 47% of those had incorporated tritium, while the percentage of tritium-positive uninfected cells did not change (1%). These results demonstrate directly that HIV-1 DNA does not colocalize with [3H]thymidine and support the notion that cell proliferation is not required for HIV-1 infection of macrophages.