Chronic obstructive pulmonary disease in adults with human immunodeficiency virus infection: a systematic review

Andreoli

et al. 2022

Sci Rep

With highly active anti-retroviral therapy (HAART), higher incidence of airway abnormalities is common in the HIV population consistent with the concept of accelerated lung “aging”. Our previous findings demonstrated that HIV induces human airway basal cells (BC) into destructive and inflammatory phenotypes. Since BC function as stem/progenitor cells of the small airway epithelium (SAE), responsible for self-renewal and differentiation of SAE, we hypothesized that BC from people living with HIV (PLWH) may have altered differentiation capacity that contribute to premature aging. The data demonstrates that BC from PLWH have impaired capacity to differentiate in vitro and senescent phenotypes including shortened telomeres, increased expression of β-galactosidase and cell cycle inhibitors, and mitochondrial dysfunction. In vitro studies demonstrated that BC senescence is partly due to adverse effects of HAART on BC. These findings provide an explanation for higher incidence of airway dysfunction and accelerated lung aging observed in PLWH.

Section: Discussionmentioning

confidence: 99%

Impaired differentiation of small airway basal stem/progenitor cells in people living with HIV

Andreoli

et al. 2022

Sci Rep

“…However, chronic HIV-1 infection is associated with several comorbid disorders, including a high incidence of chronic obstructive pulmonary disease manifesting as emphysema (Bhatia and Chow, 2016; Bhatia et al, 2012; Crothers et al, 2006; Crothers et al, 2011; Diaz et al, 1992; Diaz et al, 2000; Diaz et al, 2003; Giantsou, 2011; Kalim et al, 2008; Morris et al, 2011a; Morris et al, 2011b; Naicker et al, 2015; Palella and Phair, 2011; Petrache et al, 2008). The pathogenesis of HIV-associated emphysema is not well understood, with some evidence implicating lung destruction mediated by alveolar macrophages, CD8 T cells, HIV envelope proteins and possibly anti-retroviral drugs (Buhl et al, 1993; George et al, 2009; Green et al, 2014; Kanmogne et al, 2005; Park et al, 2001; Plata et al, 1987; Twigg et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…HIV-1 associated emphysema was originally linked to opportunistic lung infections and intravenous drug use (Beck et al, 2001; Morris et al, 2000). A number of studies, however, have clearly demonstrated that HIV-1 + individuals who have no prior history of pulmonary infection have a higher incidence of emphysema than that of the general population and develop emphysema at an early age, i.e., infection with HIV-1 is a cofactor in the development of COPD (Crothers et al, 2006; Crothers et al, 2011; Diaz et al, 1992; Diaz et al, 2000; Diaz et al, 2003; Giantsou, 2011; Morris et al, 2011a; Morris et al, 2011b; Petrache et al, 2008). The pathogenesis of HIV-associated emphysema is not understood, with some evidence pointing to alveolar macrophage (AM) and CD8 T cell mediators (Buhl et al, 1993; Plata et al, 1987; Twigg et al, 1999), direct effects on the lung of HIV proteins such as Env and Tat (Green et al, 2014; Kanmogne et al, 2005; Park et al, 2001) and adverse effects of anti-retroviral therapies (George et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue-Destructive Phenotype

et al. 2017

Cell Reports

Summary While highly active anti-retroviral therapy has dramatically improved the survival of HIV-infected individuals, there is an increased risk for other co-morbidities, such as COPD, manifesting as emphysema. Given that emphysema orginates around the airways, and that human airway basal cells (BC) are adult airway stem/progenitor cells, we hypothesized that HIV reprograms BCs to a distinct phenotype that contribute to the development of emphysema. Our data indicate that HIV binds to, but does not replicate, in BC. HIV binding to BCs induces them to acquire an invasive phenotype, mediated by up-regulation of MMP-9 expression through activation of MAPK signaling pathways. This HIV-induced “destructive” phenotype may contribute to degradation of extracellular matrix and tissue damage relevant to the development of emphysema commonly seen in HIV+ individuals.

HIV induces airway basal progenitor cells to adopt an inflammatory phenotype

Kaner

et al. 2021

Sci Rep

Despite the introduction of anti-retroviral therapy, chronic HIV infection is associated with an increased incidence of other comorbidities such as COPD. Based on the knowledge that binding of HIV to human airway basal stem/progenitor cells (BC) induces a destructive phenotype by increased MMP-9 expression through MAPK signaling pathways, we hypothesized that HIV induces the BC to express inflammatory mediators that contribute to the pathogenesis of emphysema. Our data demonstrate that airway BC isolated from HAART-treated HIV+ nonsmokers spontaneously release inflammatory mediators IL-8, IL-1β, ICAM-1 and GM-CSF. Similarly, exposure of normal BC to HIV in vitro up-regulates expression of the same inflammatory mediators. These HIV-BC derived mediators induce migration of alveolar macrophages (AM) and neutrophils and stimulate AM proliferation. This HIV-induced inflammatory phenotype likely contributes to lung inflammation in HIV+ individuals and provides explanation for the increased incidence of COPD in HIV+ individuals.