Extracellular vesicles and chronic inflammation during HIV infection

Abstract

Inflammation is a hallmark of HIV infection. Among the multiple stimuli that can induce inflammation in untreated infection, ongoing viral replication is a primary driver. After initiation of effective combined antiretroviral therapy (cART), HIV replication is drastically reduced or halted. However, even virologically controlled patients may continue to have abnormal levels of inflammation. A number of factors have been proposed to cause inflammation in HIV infection: among others, residual (low‐level) HIV replication, production of HIV protein or RNA in the absence of replication, microbial translocation from the gut to the circulation, co‐infections, and loss of immunoregulatory responses. Importantly, chronic inflammation in HIV‐infected individuals increases the risk for a number of non‐infectious co‐morbidities, including cancer and cardiovascular disease. Thus, achieving a better understanding of the underlying mechanisms of HIV‐associated inflammation in the presence of cART is of utmost importance. Extracellular vesicles have emerged as novel actors in intercellular communication, involved in a myriad of physiological and pathological processes, including inflammation. In this review, we will discuss the role of extracellular vesicles in the pathogenesis of HIV infection, with particular emphasis on their role as inducers of chronic inflammation.

Shedding Light on the Role of Extracellular Vesicles in HIV Infection and Wound Healing

“…In the past decade, EVs have been shown to influence numerous cellular functions. Infected cells secrete EVs just as normal cells do, and during pathogenic infection, EVs secreted from infected cells carry not only host components but also pathogen-derived components [48,49]. Consequently, EVs produced from infected cells modulate the susceptibility of the receiving cell, usually by priming the cell for infection [50].…”

“…Cells infected with microorganisms, including bacteria, fungi, and viruses, produce EVs that can either modulate host immunity or enhance the severity of the infection [48,49]. The EVs produced by infected or sick cells commonly incorporate virulent factors, and, as a result, these EVs play a crucial role in spreading the infection or sickness [59,60].…”

Role of Extracellular Vesicles in Substance Abuse and HIV-Related Neurological Pathologies

“…HIV is particularly hard to treat due to its ability to amass beyond the blood-brain barrier; it has a wide variety of impacts on the brain, including increased EV release [161,162]. Recently, research has investigated the role EVs play in the progression of microglia-mediated inflammation of HIV-infected subjects [151,161,163]. This inflammatory state is not resolved by combination antiretroviral therapy (cART) and remains a persisting issue [151].…”

“…Recently, research has investigated the role EVs play in the progression of microglia-mediated inflammation of HIV-infected subjects [151,161,163]. This inflammatory state is not resolved by combination antiretroviral therapy (cART) and remains a persisting issue [151]. Currently, METH is being investigated for its potential role in exacerbating HIV-mediated inflammation due to its ability to increase vesicular shedding and extracellular release [98,159,164,165].…”

<p>Extracellular Vesicle-Related Thrombosis in Viral Infection</p>

“…146 EVs after HIV infection have a significant influence on the immune system. [147][148][149] CMVrelated EVs are useful to reinforce infectivity of CMV. 143,150 Human CMV infection is controlled by T cell-mediated immunity and CMV infects ECs.…”