HIV-1 induces extensive changes in its host cell's nuclear pores, Monette et al. reveal.
Like all viruses, HIV-1 hijacks the molecular machinery of its host cell to drive its own replication. One process disrupted by the virus is protein transport between the nucleus and cytoplasm. For example, HIV-1 prevents an RNA-binding protein called hnRNP A1 from entering the nucleus so that it can bind to the virus’ RNA in the cytoplasm and initiate production of viral proteins. To learn more about HIV-1’s effects on nucleocytoplasmic transport, Monette et al. isolated the nuclear envelopes of infected cells and analyzed their protein composition by mass spectrometry.
Viral infection altered the abundance of many nuclear envelope proteins, including the nuclear pore components called nucleoporins. At least one of these pore proteins—Nup62—relocalized to the cytoplasm of HIV-1–infected cells and was even incorporated into new HIV-1 virions budding from the plasma membrane. Nup62 is dislodged from nuclear pores at a late stage of the viral life cycle, when the virus’ RNA is transported out of the nucleus. Viruses lacking the nuclear export protein Rev were unable to displace Nup62 into the cytoplasm. On the other hand, viral RNA was retained in the nuclei of host cells lacking Nup62, decreasing viral production and infectivity.
Author Andrew Mouland now wants to investigate whether the incorporation of Nup62 into budding virions aids their ability to infect new cells, for example by assisting the entry of viral genetic material into the nucleus. If so, a dual involvement in both early and late stages of HIV-1’s life cycle would make Nup62 an attractive therapeutic target.