Cell entry by enveloped viruses: redox considerations for HIV and SARS-coronavirus.
For enveloped viruses, genome entry into the target cell involves two major steps: virion binding to the cell-surface receptor and fusion of the virion and cell membranes. Virus-cell membrane fusion is mediated by the virus envelope complex, and its fusogenicity is the result of an active virus-cell interaction process that induces conformation changes within the envelope. For some viruses, such as influenza, exposure to an acidic milieu within the cell during the early steps of infection triggers the necessary structural changes. However, for other pathogens which are not exposed to such environmental stress, activation of fusogenicity can result from precise thiol/disulfide rearrangements mediated by either an endogenous redox autocatalytic isomerase or a cell-associated oxidoreductase. Study of the activation of HIV envelope fusogenicity has revealed new knowledge about how redox changes within a viral envelope trigger fusion. We discuss these findings and their implication for anti-HIV therapy. In addition, to compare and contrast the situation outlined for HIV with an enveloped virus that can fuse with the cell plasma membrane independent of the redox status of its envelope protein, we review parallel data obtained on SARS coronavirus entry.
Fenouillet
Emmanuel
E
CNRS FRE2738 and Université de la Méditerranée, Faculté de Médecine, Marseille, France. emmanuel.fenouillet@univmed.fr
Barbouche
Rym
R
Jones
Ian M
IM
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D004220:Disulfides / Q000737:chemistry; D006678:HIV / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000378:metabolism; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*
D015704:CD4 Antigens; D004220:Disulfides; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41