The temperature arrested intermediate of virus-cell fusion is a functional step in HIV infection.
HIV entry occurs via membrane-mediated fusion of virus and target cells. Interactions between gp120 and cellular co-receptors lead to both the formation of fusion pores and release of the HIV genome into target cells. Studies using cell-cell fusion assays have demonstrated that a temperature-arrested state (TAS) can generate a stable intermediate in fusion related events. Other studies with MLV pseudotyped with HIV envelope also found that a temperature sensitive intermediate could be generated as revealed by the loss of a fluorescently labeled membrane. However, such an intermediate has never been analyzed in the context of virus infection. Therefore, we used virus-cell infection with replication competent HIV to gain insights into virus-cell fusion. We find that the TAS is an intermediate in the process culminating in the HIV infection of a target cell. In the virion-cell TAS, CD4 has been engaged, the heptad repeats of gp41 are exposed and the complex is kinetically predisposed to interact with coreceptor to complete the fusion event leading to infection.
Henderson
Hamani I
HI
University of Illinois @ Chicago, Department of Microbiology and Immunology, Chicago, IL 60612, USA. hamani@northwestern.edu
Hope
Thomas J
TJ
D001596:Benzylamines; D001665:Binding Sites / Q000502:physiology; D016860:CD4 Immunoadhesins / Q000494:pharmacology; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003080:Cold Temperature; D000080027:Cyclams; D015700:HIV Envelope Protein gp41 / Q000378:metabolism / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D013997:Time Factors; D001616:beta-Galactosidase / Q000032:analysis / Q000096:biosynthesis
D001596:Benzylamines; D016860:CD4 Immunoadhesins; C096753:CD4-IgG(2); D000080027:Cyclams; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D006571:Heterocyclic Compounds; D010446:Peptide Fragments; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C407149:peptide C34; D001616:beta-Galactosidase; C088327:plerixafor