Abstract
The incorporation of biologically active host proteins into HIV-1 is a well-established phenomenon, particularly due to the budding mechanism of viral egress in which viruses acquire their external lipid membrane directly from the host cell. While this mechanism might seemingly imply that host protein incorporation is a passive uptake of all cellular antigens associated with the plasma membrane at the site of budding, this is not the case. Herein, we review the evidence indicating that host protein incorporation can be a selective and conserved process. We discuss how HIV-1 virions displaying host proteins on their surface can exhibit a myriad of altered phenotypes, with notable impacts on infectivity, homing, neutralization, and pathogenesis. This review describes the canonical and emerging methods to detect host protein incorporation, highlights the well-established host proteins that have been identified on HIV-1 virions, and reflects on the role of these incorporated proteins in viral pathogenesis and therapeutic targeting. Despite many advances in HIV treatment and prevention, there remains a global effort to develop increasingly effective anti-HIV therapies. Given the broad range of biologically active host proteins acquired on the surface of HIV-1, additional studies on the mechanisms and impacts of these incorporated host proteins may inform the development of novel treatments and vaccine designs.
Highlights
Enveloped viruses are a subset of virions that contain a lipid envelope derived from the cellular membranes of their hosts and are the etiologic agents of many of the deadliest human diseases, including Ebola, influenza, and human immunodeficiency virus (HIV)/AIDS [1,2,3]
human lymphocyte antigen (HLA)-DR has consistently been found at high levels on the surface of HIV-1 virions derived from multiple cell types, despite it not being avidly expressed on host cell membranes [18,54]
The number of host-derived HLA-DR and β-2 microglobulin molecules associated with simian immunodeficiency virus (SIV) and HIV-1 virions were found to outnumber the viral envelope glycoproteins [15], additional evidence suggesting that virions are enriched for select host proteins [12,17]
Summary
Enveloped viruses are a subset of virions that contain a lipid envelope derived from the cellular membranes of their hosts and are the etiologic agents of many of the deadliest human diseases, including Ebola, influenza, and HIV/AIDS [1,2,3]. Very early studies suggested that host proteins were present in the envelopes of animal viruses such as the avian myeloblastosis virus and in murine leukemia virus [7,8,9], but minimal biological significance was attributed to these findings. In these early studies it was noted that the host-derived ATPase proteins in the myeloblastosis virion envelope remained functionally active [7,9], demonstrating that host proteins. This review will highlight host proteins that are well-established to be incorporated into HIV-1 virions, tools used to identify host protein incorporation, and lastly, how these incorporated proteins can influence viral pathogenesis and could be targeted in novel therapeutics
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