4.8 Review

Pulmonary Immune Dysregulation and Viral Persistence During HIV Infection

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.808722

Keywords

HIV; HIV reservoir; pulmonary immunity; lungs; alveolar macrophages; CD8 T-cell dysfunction; mucosal immunity; alveolar macrophage (AM)

Categories

Funding

  1. Canadian Institutes of Health Research (CIHR) [153082]
  2. CIHR [HB2-164064]
  3. Reseau SIDA et maladies infectieuses du Fonds de recherche du Quebec-Sante (FRQ-S)
  4. FRQ-S
  5. FRQS Junior 2 Clinician-researcher salary award
  6. CIHR Canada Research Chair tier 2 in Immuno-Virology

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Despite successful antiretroviral therapy, people living with HIV still experience a higher rate of respiratory infections, lung cancers, and chronic lung disease. The lung mucosa, previously overlooked as an HIV reservoir site, plays a significant role in this phenomenon. Residual levels of HIV in deep tissues, combined with chronic immune activation and pulmonary inflammation, contribute to viral persistence. Factors such as smoking, gut and lung dysbiosis, and co-infections further exacerbate residual viral replication and inflammation.
Despite the success of antiretroviral therapy (ART), people living with HIV continue to suffer from high burdens of respiratory infections, lung cancers and chronic lung disease at a higher rate than the general population. The lung mucosa, a previously neglected HIV reservoir site, is of particular importance in this phenomenon. Because ART does not eliminate the virus, residual levels of HIV that remain in deep tissues lead to chronic immune activation and pulmonary inflammatory pathologies. In turn, continuous pulmonary and systemic inflammation cause immune cell exhaustion and pulmonary immune dysregulation, creating a pro-inflammatory environment ideal for HIV reservoir persistence. Moreover, smoking, gut and lung dysbiosis and co-infections further fuel the vicious cycle of residual viral replication which, in turn, contributes to inflammation and immune cell proliferation, further maintaining the HIV reservoir. Herein, we discuss the recent evidence supporting the notion that the lungs serve as an HIV viral reservoir. We will explore how smoking, changes in the microbiome, and common co-infections seen in PLWH contribute to HIV persistence, pulmonary immune dysregulation, and high rates of infectious and non-infectious lung disease among these individuals.

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