Mammalian cells contain intrinsic factors, such as APOBEC3, SAMHD1 and TRIM5-α, that restrict pathogenic infection with HIV-1. In Nature, Malim and colleagues identify MX2 as another potent inhibitor of such infection, which is induced by interferon-α signaling. MX2, a GTPase known to accumulate at the cytoplasmic face of nuclear pores, may block nuclear uptake of viral replication complexes or decrease their stability. MX2 has high selectivity for primate lentiviruses, and its ability to inhibit HIV-1 replication is dependent on the presence of the viral capsid protein and partially dependent on its GTP-binding domain. MX1, the protein most closely related to MX2, inhibits a variety of RNA and DNA viruses, including influenza A virus, but has no effect on HIV-1. The mechanism by which MX2 interferes with infection by HIV-1 remains unclear.

Nature (18 September 2013) doi:10.1038/nature12542