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.
Highlights
Human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses that are the causative agents of Acquired Immune Deficiency Syndrome (AIDS)
We investigated the cellular distribution of HIV-1 and -2 Gag using confocal immunofluorescence microscopy of cells transfected with doi:10.1371/journal.pone.0158941.g001
Given the possibility that AP-3 may function in the trafficking of HIV-2 Gag between intracellular compartments and the cell surface, we looked at whether AP-3 co-localized with HIV-1 or HIV-2 Gag
Summary
Human immunodeficiency virus (HIV) types 1 and 2 are closely related lentiviruses that are the causative agents of Acquired Immune Deficiency Syndrome (AIDS). The majority of patients infected with HIV-1 will develop AIDS within 8–10 years of infection, whereas only a minority of patients infected with HIV-2 will develop AIDS, and over a longer timespan [1, 2]. HIV-2 is less transmissible than HIV-1 [3], and has not spread widely from West Africa. These differences are likely a consequence of the different levels of virus found in patients during the clinically asymptomatic phase of HIV-1 or -2 infection [4]. Cohort studies have shown that circulating viral loads of HIV-2 are lower than HIV-1 during infection, PLOS ONE | DOI:10.1371/journal.pone.0158941. Cohort studies have shown that circulating viral loads of HIV-2 are lower than HIV-1 during infection, PLOS ONE | DOI:10.1371/journal.pone.0158941 July 8, 2016
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.