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Viruses
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The Role of Cytokines in HIV Infection
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The Role of Cytokines in HIV Infection

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 9975

Special Issue Editor

Dr. Christophe Vanpouille

E-Mail Website
Guest Editor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD, USA
Interests: HIV; extracellular vesicles; CMV

Special Issue Information

Dear Colleagues,

Cytokines are part of the language used by the innate and adaptive immune system to orchestrate an effective immune response to infectious pathogens. Infection with HIV results in dysregulation of the cytokine profile, which contributes to the pathogenesis of the disease by impairing cell-mediated immunity. The profound disruption of the cytokine/chemokine network is observed both in blood and genital secretions of people living with HIV.

Although antiretroviral treatment has improved the life expectancy of people with HIV, many cytokine/chemokine perturbations persist during treatment. These perturbations not only act as a marker but also contribute to persistent inflammation during HIV infection, which is associated with accelerated disease progression, end-organ diseases, and increased mortality.

This Special Issue is dedicated to the effects of HIV infection on cytokine perturbations.

Dr. Christophe Vanpouille
Guest Editor

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Keywords

  • HIV
  • cytokines
  • innate and adaptive immune system
  • HIV treatment

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Published Papers (5 papers)

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Research

20 pages, 2847 KiB  
Article
Unique Profile of Proinflammatory Cytokines in Plasma of Drug-Naïve Individuals with Advanced HIV/TB Co-Infection
by Marina Nosik, Maria G. Belikova, Konstantin Ryzhov, Darya Avdoshina, Alexandr Sobkin, Vitaly Zverev and Oxana Svitich
Viruses 2023, 15(6), 1330; https://doi.org/10.3390/v15061330 - 6 Jun 2023
Cited by 5 | Viewed by 1721
Abstract
HIV-1 infection is characterized by aberrant immune activation, and infection with M. tuberculosis by an unbalanced production of proinflammatory cytokines. The expression of these cytokines in HIV-1/TB coinfection is still understudied. Here, we aimed to compare the production of proinflammatory cytokines in drug-naive [...] Read more.
HIV-1 infection is characterized by aberrant immune activation, and infection with M. tuberculosis by an unbalanced production of proinflammatory cytokines. The expression of these cytokines in HIV-1/TB coinfection is still understudied. Here, we aimed to compare the production of proinflammatory cytokines in drug-naive patients coinfected with HIV-1 and M. tuberculosis (HIV/TB) compared to patients with respective monoinfections. Plasma samples of patients with HIV/TB coinfection (n = 36), HIV-1 monoinfection (n = 36), and TB monoinfection (n = 35) and healthy donors (n = 36) were examined for the levels of eight proinflammatory cytokines. Their levels were significantly increased in all patient groups compared to healthy donors. At the same time, a drastic decrease in the plasma levels of IFN-γ, TNF-α, Il-1β, IL-15, and IL-17 was detected in patients with HIV/TB coinfection compared to patients with HIV-1 or TB monoinfections. The plasma levels of IL-17 characterized the TB severity: in HIV/TB-coinfected patients with disseminated TB, plasma levels of IL-17 were eight times lower than in patients with less severe TB forms (infiltrative TB or TB of intrathoracic lymph nodes; p < 0.0001). At the same time, HIV/TB-coinfected patients had increased plasma levels of IL-8, IL-12, and IL-18, with the levels of IL-8 correlating with mortality (p < 0.0001). Thus, on the contrary to the patients with HIV-1 or TB monoinfections, HIV/TB-coinfected patients had suppressed production of most of the proinflammatory cytokines associated with antimicrobial immune response, specifically of T-cells involved in the containment of both infections. At the same time, they demonstrated an expansion of proinflammatory cytokines known to originate from both hematopoietic and nonhematopoietic cells, and manifest tissue inflammation. In HIV-1/TB coinfection, this leads to the disruption of granuloma formation, contributing to bacterial dissemination and enhancing morbidity and mortality. Full article
(This article belongs to the Special Issue The Role of Cytokines in HIV Infection)
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15 pages, 2910 KiB  
Article
Systemic, Mucosal Immune Activation and Psycho-Sexual Health in ART-Suppressed Women Living with HIV: Evaluating Biomarkers and Environmental Stimuli
by Parni Nijhawan, Anna Carraro, Serena Vita, Cosmo Del Borgo, Eeva Tortellini, Mariasilvia Guardiani, Maria Antonella Zingaropoli, Fabio Mengoni, Vincenzo Petrozza, Luciana Di Troia, Immacolata Marcucci, Blerta Kertusha, Maria Cristina Scerpa, Ombretta Turriziani, Vincenzo Vullo, Maria Rosa Ciardi, Claudio Maria Mastroianni, Raffaella Marocco and Miriam Lichtner
Viruses 2023, 15(4), 960; https://doi.org/10.3390/v15040960 - 13 Apr 2023
Cited by 1 | Viewed by 1674
Abstract
Gender medicine is now an approach that can no longer be neglected and must be considered in scientific research. We investigated the systemic and mucosal immune response in a population of women living with HIV (WLWH) who were receiving successful ART and the [...] Read more.
Gender medicine is now an approach that can no longer be neglected and must be considered in scientific research. We investigated the systemic and mucosal immune response in a population of women living with HIV (WLWH) who were receiving successful ART and the sexual and psychological repercussions of HIV infection on the women’s health. As control group, healthy women (HW) matched for age and sex distribution, without any therapy, were included. In summary, our study highlighted the persistence of immune-inflammatory activation in our population, despite virological suppression and a normal CD4 cell count. We found a hyperactivation of the systemic monocyte and an increase in inflammatory cytokine concentrations at the systemic level. The analysis carried out showed a significantly higher risk of HPV coinfection in WLWH compared to HW. Furthermore, our data revealed that WLWH have a profile compatible with sexual dysfunction and generalized anxiety disorders. Our study underlines that patients living with HIV should be evaluated by multidisciplinary teams. These findings also support the idea that more and different immunological markers, in addition to those already used in clinical practice, are needed. Further studies should be carried out to clarify which of these could represent future therapy targets. Full article
(This article belongs to the Special Issue The Role of Cytokines in HIV Infection)
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13 pages, 1191 KiB  
Article
CD8+ Lymphocytes from Healthy Blood Donors Secrete Antiviral Levels of Interferon-Alpha
by Fernando Teque, Abby Wegehaupt, Ellen Roufs and M. Scott Killian
Viruses 2023, 15(4), 894; https://doi.org/10.3390/v15040894 - 30 Mar 2023
Viewed by 1423
Abstract
The adaptive immune response to viral infections features the antigen-driven expansion of CD8+ T cells. These cells are widely recognized for their cytolytic activity that is mediated through the secretion of cytokines such as perforin and granzymes. Less appreciated is their ability to [...] Read more.
The adaptive immune response to viral infections features the antigen-driven expansion of CD8+ T cells. These cells are widely recognized for their cytolytic activity that is mediated through the secretion of cytokines such as perforin and granzymes. Less appreciated is their ability to secrete soluble factors that restrict virus replication without killing the infected cells. In this study we measured the ability of primary anti-CD3/28-stimulated CD8+ T cells from healthy blood donors to secrete interferon-alpha. Supernatants collected from CD8+ T cell cultures were screened for their ability to suppress HIV-1 replication in vitro and their interferon-alpha concentrations were measured by ELISA. Interferon-alpha concentrations in the CD8+ T cell culture supernatants ranged from undetectable to 28.6 pg/mL. The anti-HIV-1 activity of the cell culture supernatants was observed to be dependent on the presence of interferon-alpha. Appreciable increases in the expression levels of type 1 interferon transcripts were observed following T cell receptor stimulation, suggesting that the secretion of interferon-alpha by CD8+ T cells is an antigen-driven response. In 42-plex cytokine assays, the cultures containing interferon-alpha were also found to contain elevated levels of GM-CSF, IL-10, IL-13, and TNF-alpha. Together, these results demonstrate that the secretion of anti-viral levels of interferon-alpha is a common function of CD8+ T cells. Furthermore, this CD8+ T cell function likely plays broader roles in health and disease. Full article
(This article belongs to the Special Issue The Role of Cytokines in HIV Infection)
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26 pages, 2513 KiB  
Article
Depressive-like Behavior Is Accompanied by Prefrontal Cortical Innate Immune Fatigue and Dendritic Spine Losses after HIV-1 Tat and Morphine Exposure
by Sara R. Nass, Yun K. Hahn, Michael Ohene-Nyako, Virginia D. McLane, M. Imad Damaj, Leroy R. Thacker II, Pamela E. Knapp and Kurt F. Hauser
Viruses 2023, 15(3), 590; https://doi.org/10.3390/v15030590 - 21 Feb 2023
Cited by 5 | Viewed by 2442
Abstract
Opioid use disorder (OUD) and HIV are comorbid epidemics that can increase depression. HIV and the viral protein Tat can directly induce neuronal injury within reward and emotionality brain circuitry, including the prefrontal cortex (PFC). Such damage involves both excitotoxic mechanisms and more [...] Read more.
Opioid use disorder (OUD) and HIV are comorbid epidemics that can increase depression. HIV and the viral protein Tat can directly induce neuronal injury within reward and emotionality brain circuitry, including the prefrontal cortex (PFC). Such damage involves both excitotoxic mechanisms and more indirect pathways through neuroinflammation, both of which can be worsened by opioid co-exposure. To assess whether excitotoxicity and/or neuroinflammation might drive depressive behaviors in persons infected with HIV (PWH) and those who use opioids, male mice were exposed to HIV-1 Tat for eight weeks, given escalating doses of morphine during the last two weeks, and assessed for depressive-like behavior. Tat expression decreased sucrose consumption and adaptability, whereas morphine administration increased chow consumption and exacerbated Tat-induced decreases in nesting and burrowing—activities associated with well-being. Across all treatment groups, depressive-like behavior correlated with increased proinflammatory cytokines in the PFC. Nevertheless, supporting the theory that innate immune responses adapt to chronic Tat exposure, most proinflammatory cytokines were unaffected by Tat or morphine. Further, Tat increased PFC levels of the anti-inflammatory cytokine IL-10, which were exacerbated by morphine administration. Tat, but not morphine, decreased dendritic spine density on layer V pyramidal neurons in the anterior cingulate. Together, our findings suggest that HIV-1 Tat and morphine differentially induce depressive-like behaviors associated with increased neuroinflammation, synaptic losses, and immune fatigue within the PFC. Full article
(This article belongs to the Special Issue The Role of Cytokines in HIV Infection)
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15 pages, 756 KiB  
Article
HIV but Not CMV Replication Alters the Blood Cytokine Network during Early HIV Infection in Men
by Christophe Vanpouille, Alan Wells, Jennifer M. Dan, Stephen A. Rawlings, Susan Little, Wendy Fitzgerald, Leonid Margolis and Sara Gianella
Viruses 2022, 14(8), 1833; https://doi.org/10.3390/v14081833 - 21 Aug 2022
Viewed by 1774
Abstract
Objective: CMV coinfection contributes to sustained immune activation in people with chronic HIV. In particular, asymptomatic CMV shedding in semen has been associated with increased local and systemic immune activation, even during suppressive antiretroviral therapy (ART). However, the effect of seminal CMV shedding [...] Read more.
Objective: CMV coinfection contributes to sustained immune activation in people with chronic HIV. In particular, asymptomatic CMV shedding in semen has been associated with increased local and systemic immune activation, even during suppressive antiretroviral therapy (ART). However, the effect of seminal CMV shedding in people with HIV in the earliest phase of HIV infection is not known. Methods: Using Luminex, we measured the concentration of 34 cytokines in the blood plasma of sixty-nine men who had sex with men with or without HIV and in subgroups of CMV shedders vs. non-shedders. Differences in blood plasma cytokines between groups were investigated using the multivariate supervised partial least squares discriminant analysis method. Results: Independently of CMV, we found that concentrations of IP-10, MIG, MCP-1, I-TAC 10, IL-16, and MIP-1β were modulated in the earliest phase of HIV infection compared with control individuals without HIV. In people with HIV, there was no difference in blood cytokines among CMV shedders vs. non-shedders. Conclusion: In early/acute HIV infection, asymptomatic CMV shedding in semen does not drive additional cytokine changes in blood. Early ART initiation should remain the priority, while the added benefit of CMV suppression during the various stages of HIV infection needs to be further investigated. Full article
(This article belongs to the Special Issue The Role of Cytokines in HIV Infection)
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