In addition to HIV-1–infected CD4+ T cells, macrophages may also be a key source of the viral reservoir in HIV-1–infected people. A recent study reveals details of how HIV-1 is restricted from macrophages, which might inform the design of new strategies for eradicating the HIV reservoir (J. Exp. Med. 210, 517–534 ).

The Imamichi laboratory previously showed that interleukin-27 (IL-27) inhibits HIV-1 replication in monocyte-derived macrophages. In their new study, this group sought to identify how IL-27 exerts its anti–HIV-1 effects. They found no evidence that IL-27 blocks entry of HIV-1 into macrophages but showed that macrophages induced with IL-27 produced less proviral cDNA of late HIV-1 gene products than control macrophages, suggesting that IL-27 interferes with HIV-1 replication between viral entry and reverse transcription.

Dai et al. then found that spectrin β nonerythrocyte 1 (SPTBN1) was downregulated in IL-27–treated macrophages compared with control macrophages. Knockdown of SPTBN1 in control macrophages prevented their infection by HIV-1, and overexpression of SPTBN1 in IL-27–induced macrophages rendered them susceptible to HIV-1 infection. The authors found that SPTBN1 associates with HIV-1 Gag proteins in macrophages and suggest that this interaction may be important for reverse transcription of the HIV-1 genome, but the functional relevance of the SPTBN1-Gag association still remains to be investigated in more detail. In addition, the effects of IL-27 need to be assessed in an in vivo model of HIV-1 infection.