Restriction of HIV-1 and other retroviruses by TRIM5.

Mammalian cells express a variety of innate immune proteins - known as restriction factors - which defend against invading retroviruses such as HIV-1. Two members of the tripartite motif protein family - TRIM5α and TRIMCyp - were identified in 2004 as restriction factors that recognize and inactivate the capsid shell that surrounds and protects the incoming retroviral core. Research on these TRIM5 proteins has uncovered a novel mode of non-self recognition that protects against cross-species transmission of retroviruses. Our developing understanding of the mechanism of TRIM5 restriction underscores the concept that core uncoating and reverse transcription of the viral genome are coordinated processes rather than discrete steps of the post-entry pathway of retrovirus replication. In this Review, we provide an overview of the current state of knowledge of the molecular mechanism of TRIM5-mediated restriction, highlight recent advances and discuss implications for the development of capsid-targeted antiviral therapeutics.

MxB is an interferon-induced restriction factor of human herpesviruses.

The type I interferon (IFN) system plays an important role in controlling herpesvirus infections, but it is unclear which IFN-mediated effectors interfere with herpesvirus replication. Here we report that human myxovirus resistance protein B (MxB, also designated Mx2) is a potent human herpesvirus restriction factor in the context of IFN. We demonstrate that ectopic MxB expression restricts a range of herpesviruses from the Alphaherpesvirinae and Gammaherpesvirinae, including herpes simplex virus 1 and 2 (HSV-1 and HSV-2), and Kaposi's sarcoma-associated herpesvirus (KSHV). MxB restriction of HSV-1 and HSV-2 requires GTPase function, in contrast to restriction of lentiviruses. MxB inhibits the delivery of incoming HSV-1 DNA to the nucleus and the appearance of empty capsids, but not the capsid delivery to the cytoplasm or tegument dissociation from the capsid. Our study identifies MxB as a potent pan-herpesvirus restriction factor which blocks the uncoating of viral DNA from the incoming viral capsid.