Mai: a novel HIV-1 matrix-interacting, human nuclear shuttling protein that is virion-associated and inhibits HIV-1 replication.
Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA171)
Gupta K, Siliciano RF, Ott D K. Gupta, 3032 St Paul Street, Baltimore MD 21218, United States, Tel.: +1 410 467 1492, E-mail: kgupta@mail.jhmi.edu
Active nuclear import of the HIV-1 preintegration complex (PIC) is essential for the productive infection of non-dividing cells. HIV-1's primary targets in vivo are CD4+ T cells, the majority of which are resting, and terminally differentiated tissue macrophages, rendering the ability of HIV-1 to enter the nucleus of non-dividing cells critical for viral pathogenesis and disease progression. Several factors responsible for nuclear localization of the HIV-1 PIC have been identified. Foremost among these is the HIV-1 Matrix protein (MA), which plays several critical roles throughout the viral life cycle, including nuclear import of the PIC during viral entry, and export of genomic RNA during viral assembly. We identified a novel human Matrix-interacting protein (MAI) using a yeast two-hybrid screen. MAI is highly conserved in vertebrates and is expressed in most human tissues. Like Matrix, MAI shuttles between the nucleus and cytoplasm and is efficiently incorporated into virions. MAI expression is upregulated upon activation of CD4+ T cells. Furthermore, overexpression of MAI significantly inhibits HIV-1 replication in tissue culture. We propose a role for MAI in the regulation of Matrix nuclear localization and by extension in both the nuclear import of the PIC and export of viral genomic RNA during assembly. Thus, the Matrix-MAI interaction may be important in the HIV-1 life cycle, and therefore critical for AIDS pathogenesis. If MAI is indeed essential for HIV-1 replication, it would present a novel target for rational antiviral drug design.
Keywords: AEGIS, Virus Replication, HIV-1, Virion, HIV Antigens, Gene Products, gag, Nuclear Proteins, Acquired Immunodeficiency Syndrome, Active Transport, Cell Nucleus, Cell Nucleus, Hominidae, RNA, Viral, HIV-1 Reverse Transcriptase, Antigens, CD4, T-Lymphocytes, HIV gag protein p17, Human, Animal, virology, immunology
000709
MoOrA171
