title: Human Immunodeficiency Virus Type 2 (HIV-2) Gag Is Trafficked in an AP-3 and AP-5 Dependent Manner.
abstract: Although human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses with similar replication cycles, HIV-2 infection is associated with slower progression to AIDS, a higher proportion of long term non-progressors, and lower rates of transmission than HIV-1, likely as a consequence of a lower viral load during HIV-2 infection. A mechanistic explanation for the differential viral load remains unclear but knowledge of differences in particle production between HIV-1 and HIV-2 may help to shed light on this issue. In contrast to HIV-1, little is known about the assembly of HIV-2 particles, and the trafficking of HIV-2 Gag, the structural component of the virus, within cells. We have established that HIV-2 Gag accumulates in intracellular CD63 positive compartments, from which it may be delivered or recycled to the cell surface, or degraded. HIV-2 particle release was dependent on the adaptor protein complex AP-3 and the newly identified AP-5 complex, but much less so on AP-1. In contrast, HIV-1 particle release required AP-1 and AP-3, but not AP-5. AP-2, an essential component of clathrin-mediated endocytosis, which was previously shown to be inhibitory to HIV-1 particle release, had no effect on HIV-2. The differential requirement for adaptor protein complexes confirmed that HIV-1 and HIV-2 Gag have distinct cellular trafficking pathways, and that HIV-2 particles may be more susceptible to degradation prior to release.
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Justine E
authors.initials: JE
authors.lastname: Alford
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Michela
authors.initials: M
authors.lastname: Marongiu
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Gemma L
authors.initials: GL
authors.lastname: Watkins
authors.affiliation: School of Life Sciences, University of Warwick, Coventry, United Kingdom.
authors.forename: Emma C
authors.identifier: http://orcid.org/0000-0002-3268-7084
authors.initials: EC
authors.lastname: Anderson
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000235:genetics / Q000378:metabolism*; D033966:Adaptor Protein Complex beta Subunits / Q000235:genetics / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism; D015498:HIV-2 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport; D060149:Tetraspanin 30 / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000378:metabolism*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: C439973:AP3B1 protein, human; C570280:AP5B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D033942:Adaptor Proteins, Vesicular Transport; C554586:CD63 protein, human; D060149:Tetraspanin 30; D054301:gag Gene Products, Human Immunodeficiency Virus