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Review
. 2003 Aug 4;162(3):371-5.
doi: 10.1083/jcb.200307062.

After Hrs with HIV

Affiliations
Review

After Hrs with HIV

Ali Amara et al. J Cell Biol. .

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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Figures

Figure 1.
Figure 1.
Schematic representation of Tsg101, Vps27p, Hrs, HIV Gag, and HIV Gag Δ PTAP -Hrs ΔN . 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.
Figure 2.
Figure 2.
Mimicry of Hrs function by HIV Gag. The normal function of Hrs, shown in the left panel, is to recruit Tsg101 and the ESCRT-I complex for sorting ubiquitinated (Ub) cargo into the MVB. During HIV infection, HIV Gag mimics Hrs and redirects the ESCRT machinery to the site of viral budding. In T cells (left panel), viral assembly and release occur at the plasma membrane, whereas in macrophages (center) HIV particles accumulate in late endosomes and MVBs. In DCs (right panel), HIV undergoes receptor-mediated endocytosis after binding to DC-SIGN and is recycled to the cell surface. Although the vesicular compartments involved have not been identified, macrophages and DCs may share a mechanism for releasing HIV particles upon contact with T lymphocytes.

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