Viruses have evolved various mechanisms to avoid recognition and destruction by the host immune system. By studying these mechanisms, we have learned much about how the immune system functions, and in the process, new therapeutic targets for drug development have been identified. HIV-1 has proven to be a difficult nut to crack in this regard, but a new study in Nature describes the identification of a human protein, CEM15, the function of which is suppressed by viral Vif, leading to the production of infectious virions. This interaction might be a new therapeutic target for drug development.

The Vif-deficient virions that are produced by primary T cells are non-infectious, such that T cells, and T-cell lines such as CEM, are referred to as non-permissive (NP). By contrast, other cell types, such as CEM-SS (a subclone of the CEM cell line), are termed permissive (P), because they can produce infectious Vif-deficient virions. Cell-fusion experiments have shown that the NP phenotype is dominant over the P phenotype. These data imply that a factor in the NP cells is able to influence the production of infectious Vif-deficient virions. Malim and colleagues set out to identify this factor by using a PCR-based complementary DNA subtraction strategy to compare CEM (NP) and CEM-SS (P) cells. Subtracted cDNAs were used as probes in northern-blot experiments using RNA from both NP and P cells. The authors identified a cDNA that corresponds to a gene that they have named CEM15, and the transcript was identified in all of the NP cells that were tested. Ectopic expression of CEM15 in a P cell line had no effect on the quantity of Vif-deficient HIV-1 particles produced by these cells, but instead of being infectious, the virus particles were non-infectious.

What is CEM15? Analysis of the CEM15 protein sequence showed that it has marked homology to APOBEC1 (a cytidine deaminase that specifically edits APOB mesenger RNA).

So, CEM15 seems to be responsible for the inability of NP cells to produce infectious Vif-deficient virions, which indicates that CEM15 is the cellular target of Vif. Because of the homology to APOBEC1, the authors speculate that CEM15 might affect Vif-deficient virions by means of interactions with viral RNA. Importantly, the CEM15–Vif interaction might prove to be an important therapeutic target for the development of new drugs to alter virus infectivity. But, the function of CEM15, and how Vif suppresses this function, remain to be determined.