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After Hrs with HIV.

Amara A, Littman DR - J. Cell Biol. (2003)

Bottom Line: To efficiently bud off from infected cells, HIV and other enveloped viruses hijack the host cellular machinery that is normally involved in vacuolar protein sorting and multivesicular body (MVB) biogenesis.The HIV Gag protein mimics hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), a modular adaptor protein that links membrane cargo recognition to its degradation after delivery to MVBs.In contrast to T cells, where HIV budding occurs at the plasma membrane, virus buds into vacuoles of macrophages, a process that may facilitate its spread within the infected host.

View Article: PubMed Central - PubMed

Affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.

ABSTRACT
To efficiently bud off from infected cells, HIV and other enveloped viruses hijack the host cellular machinery that is normally involved in vacuolar protein sorting and multivesicular body (MVB) biogenesis. The HIV Gag protein mimics hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), a modular adaptor protein that links membrane cargo recognition to its degradation after delivery to MVBs. In contrast to T cells, where HIV budding occurs at the plasma membrane, virus buds into vacuoles of macrophages, a process that may facilitate its spread within the infected host.

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Schematic representation of Tsg101, Vps27p, Hrs, HIV Gag, and HIV GagΔ PTAP-HrsΔN. Pro, proline rich domain; S-Box, steadiness box; VHS, Vps27-Hrs-STAM domain; FYVE, PI(3)P interaction domain; C-C, coiled-coil domain; P/Q, proline- and glutamine-rich sequence; MA, matrix; CA, capsid; NC, nucleocapsid.
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fig1: Schematic representation of Tsg101, Vps27p, Hrs, HIV Gag, and HIV GagΔ PTAP-HrsΔN. Pro, proline rich domain; S-Box, steadiness box; VHS, Vps27-Hrs-STAM domain; FYVE, PI(3)P interaction domain; C-C, coiled-coil domain; P/Q, proline- and glutamine-rich sequence; MA, matrix; CA, capsid; NC, nucleocapsid.

Mentions: The Gag protein of HIV is synthesized as a 55-kD precursor, whose NH2 terminus is myristylated, thus targeting the protein to membranes, where it forms homotypic aggregates that induce membrane invagination and budding (Freed, 1998; Gottlinger, 2001). As the budding viral particles mature, the Gag precursor is cleaved into the myristylated NH2-terminal p17MA (matrix), p24CA (capsid), p7NC (nucleocapsid), and p6 (late domain) (Freed, 1998). Studies from several laboratories in the last few years have demonstrated that a highly conserved sequence in p6, PTAP, is required for completion of viral budding (Fig. 1) (Huang et al., 1995; Freed, 1998). This motif was found to serve as a docking site for the host cellular factor tumor susceptibility gene 101 (Tsg101), a protein that, in turn, is required for release of viral particles from HIV-producing cells (Garrus et al., 2001). A ubiquitin binding domain (designated ubiquitin E2 variant sequence [UEV]) at the NH2 terminus of Tsg101 binds to the PTAP motif, and the binding is enhanced if the Gag p6 polypeptide is ubiquitinated (Garrus et al., 2001; VerPlank et al., 2001; Pornillos et al., 2002a).


After Hrs with HIV.

Amara A, Littman DR - J. Cell Biol. (2003)

Schematic representation of Tsg101, Vps27p, Hrs, HIV Gag, and HIV GagΔ PTAP-HrsΔN. Pro, proline rich domain; S-Box, steadiness box; VHS, Vps27-Hrs-STAM domain; FYVE, PI(3)P interaction domain; C-C, coiled-coil domain; P/Q, proline- and glutamine-rich sequence; MA, matrix; CA, capsid; NC, nucleocapsid.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172700&req=5

fig1: Schematic representation of Tsg101, Vps27p, Hrs, HIV Gag, and HIV GagΔ PTAP-HrsΔN. Pro, proline rich domain; S-Box, steadiness box; VHS, Vps27-Hrs-STAM domain; FYVE, PI(3)P interaction domain; C-C, coiled-coil domain; P/Q, proline- and glutamine-rich sequence; MA, matrix; CA, capsid; NC, nucleocapsid.
Mentions: The Gag protein of HIV is synthesized as a 55-kD precursor, whose NH2 terminus is myristylated, thus targeting the protein to membranes, where it forms homotypic aggregates that induce membrane invagination and budding (Freed, 1998; Gottlinger, 2001). As the budding viral particles mature, the Gag precursor is cleaved into the myristylated NH2-terminal p17MA (matrix), p24CA (capsid), p7NC (nucleocapsid), and p6 (late domain) (Freed, 1998). Studies from several laboratories in the last few years have demonstrated that a highly conserved sequence in p6, PTAP, is required for completion of viral budding (Fig. 1) (Huang et al., 1995; Freed, 1998). This motif was found to serve as a docking site for the host cellular factor tumor susceptibility gene 101 (Tsg101), a protein that, in turn, is required for release of viral particles from HIV-producing cells (Garrus et al., 2001). A ubiquitin binding domain (designated ubiquitin E2 variant sequence [UEV]) at the NH2 terminus of Tsg101 binds to the PTAP motif, and the binding is enhanced if the Gag p6 polypeptide is ubiquitinated (Garrus et al., 2001; VerPlank et al., 2001; Pornillos et al., 2002a).

Bottom Line: To efficiently bud off from infected cells, HIV and other enveloped viruses hijack the host cellular machinery that is normally involved in vacuolar protein sorting and multivesicular body (MVB) biogenesis.The HIV Gag protein mimics hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), a modular adaptor protein that links membrane cargo recognition to its degradation after delivery to MVBs.In contrast to T cells, where HIV budding occurs at the plasma membrane, virus buds into vacuoles of macrophages, a process that may facilitate its spread within the infected host.

View Article: PubMed Central - PubMed

Affiliation: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA.

ABSTRACT
To efficiently bud off from infected cells, HIV and other enveloped viruses hijack the host cellular machinery that is normally involved in vacuolar protein sorting and multivesicular body (MVB) biogenesis. The HIV Gag protein mimics hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs), a modular adaptor protein that links membrane cargo recognition to its degradation after delivery to MVBs. In contrast to T cells, where HIV budding occurs at the plasma membrane, virus buds into vacuoles of macrophages, a process that may facilitate its spread within the infected host.

Show MeSH
Related in: MedlinePlus