Regulating the functions of the HIV-1 matrix protein

AC Hearps, DA Jans - AIDS research and human retroviruses, 2007 - liebertpub.com
AC Hearps, DA Jans
AIDS research and human retroviruses, 2007liebertpub.com
The HIV-1 structural protein matrix (MA) is involved in a number of essential steps during
infection and appears to possess multiple, seemingly conflicting targeting signals. Although
MA has long been known to be crucial for virion assembly, details regarding this function,
and the domains responsible for mediating it, are still emerging. MA has also been
implicated in nuclear import of HIV cDNA and is purported to contain a nuclear targeting
signal. Little is known about how these opposing plasma membrane and nuclear targeting …
The HIV-1 structural protein matrix (MA) is involved in a number of essential steps during infection and appears to possess multiple, seemingly conflicting targeting signals. Although MA has long been known to be crucial for virion assembly, details regarding this function, and the domains responsible for mediating it, are still emerging. MA has also been implicated in nuclear import of HIV cDNA and is purported to contain a nuclear targeting signal. Little is known about how these opposing plasma membrane and nuclear targeting signals are regulated and which signals predominate at various stages of infection. Additionally, MA has recently been implicated in a number of novel roles during infection including viral entry/uncoating, cytoskeletal-mediated transport, and targeting viral assembly to lipid rafts. Here we discuss our current understanding of MA's functions during infection and explore the recent advancements made in elucidating the mechanism of these processes. It appears that MA possesses a cache of targeting signals that are likely to be regulated throughout the infectious cycle by a combination of structural and biochemical modifications including phosphorylation, myristoylation, and multimerization. The ability of HIV to modify the properties of MA at specific stages of infection is central to the multifunctional behavior of MA and the efficiency of HIV infection. The recently reported success of drugs specifically designed to block MA function (Haffar O, Dubrovsky L, and Lowe R et al. J Virol 2005;79:13028–13036) confirms the importance of this protein for HIV infection and highlights a potentially new avenue in multivalent drug therapy.
Mary Ann Liebert