Regulating the functions of the HIV-1 matrix protein.
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.
Hearps
Anna C
AC
Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
Jans
David A
DA
D015683:Gene Products, gag / Q000187:drug effects / Q000378:metabolism*; D015488:HIV Antigens / Q000187:drug effects / Q000378:metabolism*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000187:drug effects / Q000378:metabolism*; D014771:Virion / Q000378:metabolism / Q000472:pathogenicity; D054301:gag Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D015488:HIV Antigens; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1