Acquired Immunodeficiency Syndrome: Tsurutani N

Ryo A, Tsurutani N, Ohba K, Kimura R, Komano J, Nishi M, Soeda H, Hattori S, Perrem K, Yamamoto M, Chiba J, Mimaya J, Yoshimura K, Matsushita S, Honda M, Yoshimura A, Sawasaki T, Aoki I, Morikawa Y, Yamamoto N. · Department of Pathology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan. · Proc Natl Acad Sci U S A. · Pubmed #18172216 links to  free full text

Abstract: Human immunodeficiency virus type 1 (HIV-1) utilizes the macromolecular machinery of the infected host cell to produce progeny virus. The discovery of cellular factors that participate in HIV-1 replication pathways has provided further insight into the molecular basis of virus-host cell interactions. Here, we report that the suppressor of cytokine signaling 1 (SOCS1) is an inducible host factor during HIV-1 infection and regulates the late stages of the HIV-1 replication pathway. SOCS1 can directly bind to the matrix and nucleocapsid regions of the HIV-1 p55 Gag polyprotein and enhance its stability and trafficking, resulting in the efficient production of HIV-1 particles via an IFN signaling-independent mechanism. The depletion of SOCS1 by siRNA reduces both the targeted trafficking and assembly of HIV-1 Gag, resulting in its accumulation as perinuclear solid aggregates that are eventually subjected to lysosomal degradation. These results together indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.

Fukushi M, Dixon J, Kimura T, Tsurutani N, Dixon MJ, Yamamoto N. · Department of Microbiology, School of Medicine, Tokyo Medical and Dental University, Japan. · FEBS Lett. · Pubmed #9923610 No free full text.

Abstract: The nef gene of human and simian immunodeficiency virus is a key factor in acquired immunodeficiency syndrome pathogenesis and virus replication. Several Nef-induced phenomena, including the down-regulation of CD4 molecule, have been previously reported. In this study, we have identified and cloned a novel cellular protein Naf1 (Nef-associated factor 1), which associated with Nef in the yeast two-hybrid system and pull-down assay. The Naf1 gene generates two isoforms (Naf1alpha and beta) containing four coiled-coil structures. The Naf1 mRNA is ubiquitously expressed in human tissues with strong expression in peripheral blood lymphocytes and spleen. Naf1 overexpression increased cell surface CD4 expression. Nef suppressed this Naf1-induced augmentation of CD4 expression, providing a novel mode of Nef action in CD4 down-regulation.