Showing papers by "Jun Komano published in 2005"

Role of the Specific Amino Acid Sequence of the Membrane-Spanning Domain of Human Immunodeficiency Virus Type 1 in Membrane Fusion

Abstract: Fusion between cell and virus membranes mediated by gp41 initiates the life cycle of human immunodeficiency virus type 1. In contrast to the many studies that have elucidated the structure-function relationship of the ectodomain, the study of the membrane-spanning domain (MSD) has been rather limited. In particular, the role that the MSD's specific amino acid sequences may have in membrane fusion as well as other gp41 functions is not well understood. The MSD of gp41 contains well-conserved glycine residues that form the GXXXG motif (G, glycine; X, other amino acid residues), a motif often found at the helix-helix interface of membrane spanning α-helices. Here we examined the role that the specific amino acid sequence of the gp41 MSD has in gp41 function, particularly in membrane fusion, by making two types of MSD mutants: (i) glycine substitution mutants in which glycine residues of the MSD were mutated to alanine or leucine residues, and (ii) replacement mutants in which the entire MSD was replaced with one derived from glycophorin A or from vesicular stomatitis virus G. The substitution of glycines did not affect gp41 function. MSD-replacement mutants, however, showed severely impaired fusion activity. The assay using the Env expression vector revealed defects in membrane fusion after CD4 binding steps in the MSD-replacement mutants. In addition, the change in Env processing was noted for MSD-replacement mutants. These results suggest that the MSD of gp41 has a relatively wide but not unlimited tolerance for mutations and plays a critical role in membrane fusion as well as in other steps of Env biogenesis.

The interaction of HIV-1 with the host factors.

Abstract: Human immunodeficiency virus type 1 (HIV-1) is a causative agent of acquired immunodeficiency syndrome (AIDS) in humans. In the last decade, the functions of HIV-1-encoded genes have been intensively studied. These studies have contributed to the development of the effective anti-AIDS drugs directing against the HIV-1-encoded enzymes, namely reverse transcriptase and protease. However, even the combination of these drugs is not sufficient enough to stop the progression of AIDS partly due to the emergence of drug-resistant HIV-1 mutants as well as the severe side effects. Understanding the molecular mechanisms by which cellular factors support the efficient replication of HIV-1 should contribute to develop means to control the progression of AIDS. This field is now expanding rapidly. Here we review the host factors involved in the replication of HIV-1 and highlight some findings that have a substantial impact on the retroviral research.