HOST PROTEIN INCORPORATION IN HUMAN IMMUNODEFICIENCY VIRUS-1
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Human Immunodeficiency Virus (HIV) incorporates a number of host proteins. These proteins can provide information on the function of viral proteins, as well as on the general process of HIV biogenesis. Determining the methods of incorporation and potential functional importance will help advance our knowledge of the HIV lifecycle and holds the potential to produce additional targets for antiretroviral therapy. Here, we used a variety of complementary techniques to determine which host proteins are incorporated into HIV particles. We found that most of the CD28 and B7 family costimulatory molecules are excluded from viral particles. Using a novel purification technique and mass spectrometry analyses, we were able to characterize host protein incorporation in HIV particles derived from CD4+ T-cell lines; we compared this data set to a reprocessed data set of monocyte-derived macrophages derived HIV-1 using the same bioinformatics pipeline. Seventy-nine clustered proteins were shared between the data sets. These clusters included an extensive collection of actin isoforms, HLA proteins, chaperones, ERM proteins, EH4, a phosphodiesterase, cyclophilin A, and others. As these proteins are incorporated in virions produced in both cell types, we hypothesize that these proteins may have direct interactions with viral proteins or may be important in the viral lifecycle. Additionally, this common protein set protein is predicted to interact with >1000 related proteins. Many of these secondary interacting proteins are reported to be incorporated into virions. Thus, only a few direct interactions between host and viral proteins may drive host protein composition in virions. We hypothesized that these may be driven by the tetraspanin family of proteins, putative membrane organizers determining the lipid and protein composition of tetraspanin enriched membranes. We found that knockdown of various tetraspanins in T cell lines did not significantly alter viral release or phenotype. Ultimately, cell type-specific differences in host protein interaction and expression may drive virion phenotypic diversity, despite conserved primary viral protein-host protein interactions across cell types. Further, the primary interactions found between viral and host proteins are likely driven by selective pressures including response to host restriction factors and membrane structural requirements.