HIV-HPV interactions via extracellular vesicles among tobacco smokers and nonsmokers

TL;DR

This study explores how HIV and HPV interact through extracellular vesicles, and how smoking affects these interactions, potentially influencing immune responses.

Contribution

The study reveals how HIV and HPV co-infection, along with smoking, alters extracellular vesicle characteristics and cytokine packaging, offering new insights into immune modulation.

Findings

HIV infection increases EV formation and modifies their protein composition.

HPV co-infection influences cytokine packaging in EVs, particularly enriching MCP-1 and RANTES.

Smoking increases EV size and inflammatory mediator packaging, such as MCP-1 and IL-18.

Abstract

Human Immunodeficiency Virus (HIV) and Human Papillomavirus (HPV) co-infections are significantly prevalent, especially among African Americans (AA), a situation further compounded by the prevalence of tobacco smoking. Extracellular vesicles (EVs) are integral to the mechanisms of viral pathogenesis, as they are pivotal in the modulation of immune responses and the inflammatory process. This research study examines the varying concentrations of EVs, their associated biomarkers, and the cytokine/chemokine profiles present in plasma obtained from individuals infected with HIV and those coinfected with HIV and HPV, with particular emphasis on the ramifications of smoking behavior. Our findings revealed that HIV infection markedly elevates EV formation and modifies their protein composition, whereas HPV co-infection does not significantly augment EV levels but does influence the specific cytokine packaging. Notably, monocyte chemoattractant protein-1 (MCP-1 or CCL2) and Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES or CCL5) exhibited substantial enrichment in EVs derived from individuals coinfected with HIV and HPV, implying a potential role of EVs in immune modulation related to viral persistence. Importantly, smoking was found to affect EV characteristics, resulting in an increase in EV size and the packaging of inflammatory mediators, such as MCP-1 and interleukin-18 (IL-18), from plasma into EVs in HIV- and/or HIV+HPV-infected samples. This observation suggests that oxidative stress induced by smoking may intensify immune dysregulation through modifications in EV-mediated cytokine signaling pathways. Nevertheless, smoking did not exhibit a significant impact on the expression of EV marker proteins or the overall levels of EVs. These outcomes underscore the intricate interactions between HIV, HPV, and/or smoking in influencing the immune milieu via EVs. Further comprehensive understanding of the role of EVs in the context of these viral infections could yield valuable insights into potential biomarkers for disease progression and new therapeutic strategies.

An illustration of key findings in extracellular vesicles (EV) and plasma in conditions involving HIV, HPV, and smoking. HIV infection increases protein levels and MCP1 in EV and decreases MCP1 and IL-8 plasma levels. Tobacco smoking leads to increases in EV size whereas MCP1 levels in EV and plasma are unchanged. Concurrent HPV infection increases EV RANTES and plasma levels of IL-18 without affecting plasma MCP1 deficiencies. Smoking in people with both HIV and HPV infections increases EV size as for HIV smokers and EV RANTES as for HIV-HPV infections. Interestingly, plasma IL-18 and MCP1 levels are reversed.

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