Vehicles of intercellular communication: exosomes and HIV-1

The terms extracellular vesicles, microvesicles, oncosomes, or exosomes are often used interchangeably as descriptors of particles that are released from cells and comprise a lipid membrane that encapsulates nucleic acids and proteins. Although these entities are defined based on a specific size range and/or mechanism of release, the terminology is often ambiguous. Nevertheless, these vesicles are increasingly recognized as important modulators of intercellular communication. The generic characterization of extracellular vesicles could also be used as a descriptor of enveloped viruses, highlighting the fact that extracellular vesicles and enveloped viruses are similar in both composition and function. Their high degree of similarity makes differentiating between vesicles and enveloped viruses in biological specimens particularly difficult. Because viral particles and extracellular vesicles are produced simultaneously in infected cells, it is necessary to separate these populations to understand their independent functions.

University of Iowa researchers summarize current understanding of the similarities and differences of extracellular vesicles, which henceforth they refer to as exosomes, and the enveloped retrovirus, HIV-1. The researchers focus on the presence of these particles in semen, as these are of particular importance during HIV-1 sexual transmission. While there is overlap in the terminology and physical qualities between HIV-1 virions and exosomes, these two types of intercellular vehicles may differ depending on the bio-fluid source. Recent data have demonstrated that exosomes from human semen serve as regulators of HIV-1 infection that may contribute to the remarkably low risk of infection per sexual exposure.

Semen exosomes inhibit HIV-1 lifecycle steps. Schematic of the HIV-1 lifecycle

exosomes

(1) HIV-1 virions bind to cell receptor/co-receptor. (2) Fusion and entry inserts the viral core in the cell cytoplasm. (3) The viral genome is reverse transcribed from single-stranded RNA to double-stranded DNA. (4) Viral double-stranded DNA is imported into the cell nucleus. (5) Viral double-stranded DNA is integrated into host double-stranded DNA. (6) Viral RNA is transcribed from integrated DNA. Concurrently, (7A) viral proteins are translated from viral RNA and (7B) progeny virions are assembled with viral proteins and viral RNA. (8) New HIV-1 virions bud from the cell plasma membrane. Semen exosomes inhibit HIV-1 at the steps of reverse transcription, proviral integration and viral transcription. See text for references.

Welch JL, Stapleton JT, Okeoma CM. (2019) Vehicles of intercellular communication: exosomes and HIV-1. J Gen Virol [Epub ahead of print]. [abstract]

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