Abstract
BackgroundEnveloped viruses including the simian immunodeficiency virus (SIV) replicating within host cells acquire host proteins upon egress from the host cells. A number of studies have catalogued such host proteins, and a few have documented the potential positive and negative biological functions of such host proteins. The studies conducted herein utilized proteomic analysis to identify differences in the spectrum of host proteins acquired by a single source of SIV replicating within CD4+ T cells from disease resistant sooty mangabeys and disease susceptible rhesus macaques.ResultsWhile a total of 202 host derived proteins were present in viral preparations from CD4+ T cells from both species, there were 4 host-derived proteins that consistently and uniquely associated with SIV replicating within CD4+ T cells from rhesus macaques but not sooty mangabeys; and, similarly, 28 host-derived proteins that uniquely associated with SIV replicating within CD4+ T cells from sooty mangabeys, but not rhesus macaques. Of interest was the finding that of the 4 proteins uniquely present in SIV preparations from rhesus macaques was a 26 S protease subunit 7 (MSS1) that was shown to enhance HIV-1 'tat" mediated transactivation. Among the 28 proteins found in SIV preparations from sooty mangabeys included several molecules associated with immune function such as CD2, CD3ε, TLR4, TLR9 and TNFR and a bioactive form of IL-13.ConclusionsThe finding of 4 host proteins that are uniquely associated with SIV replicating within CD4+ T cells from disease susceptible rhesus macaques and 28 host proteins that are uniquely associated with SIV replicating within CD4+ T cells from disease resistant sooty mangabeys provide the foundation for determining the potential role of each of these unique host-derived proteins in contributing to the polarized clinical outcome in these 2 species of nonhuman primates.
Highlights
Enveloped viruses including the simian immunodeficiency virus (SIV) replicating within host cells acquire host proteins upon egress from the host cells
The first detailed study aimed at cataloging the types of host proteins that become associated with HIV-1 was performed by Chertova et al [19] who utilized LC/MS/MS analysis of HIV1 preparations isolated from infection of enriched populations of human monocyte derived macrophages
A series of primary day 3 Con-A blasts from 3 individual rhesus macaques (RM) and 3 individual sooty mangabeys (SM) were utilized for infection with a SIVdelTable 670 sub-stock, which replicated well in cells from both species
Summary
Enveloped viruses including the simian immunodeficiency virus (SIV) replicating within host cells acquire host proteins upon egress from the host cells. While SIV carry with them parts of the plasma membrane containing host proteins some of which remain stably associated with the virions The role these host proteins play while associated with the virions on the infectivity of the virus and/or on the host immune system remains incompletely understood. The initial studies were focused on identifying the mere physical presence of host proteins that had previously been identified as playing a role in immune function [7,8] These studies were soon followed by reports showing that several of these host proteins, such as the MHC class II proteins, ICAM-1, CD28 and CD40L, could enhance the infectivity of the virions, for some as much as 20 to 100-fold with target cells that expressed the cognate receptors for such molecules [9,10,11,12,13]. A rather substantial list of > 250 host proteins were identified along with 26 of the 37 host proteins previously found to be associated with exosomes
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