Editors' ChoiceHIV

That silent alliance: HIV and smoke promote lung diseases

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Science Translational Medicine  24 Oct 2018:
Vol. 10, Issue 464, eaav3893
DOI: 10.1126/scitranslmed.aav3893


Smoking and HIV independently and synergistically promote pathophysiological changes consistent with chronic lung disease in macaques.

Thanks to recent therapeutic advancements, the life span of people with human immunodeficiency virus (HIV) infection dramatically increased. However, pulmonary disorders are becoming a major health care burden for patients with HIV. Subjects with HIV have higher prevalence of smoking, and epidemiological data has suggested that HIV is independently associated with the development of chronic obstructive pulmonary diseases (COPD). Importantly, the lung is known to be a reservoir for HIV, even despite appropriate immunological reconstitution and viremia control with antiretroviral therapy (ART). However, the mechanisms by which HIV independently affects the risk of developing pulmonary disorders are not well understood.

In this study, Chand et al. used a nonhuman primate model to evaluate the independent and synergic effects of HIV and smoking in the development of chronic bronchitis. Female macaques were exposed to whole body smoke 6 hours per day, 5 days a week for 27 weeks. During that time, a subgroup was then infected with simian-adapted human immunodeficiency virus (SHIV) and treated subcutaneously with ART (tenofovir and emtricitabine). Cigarette smoke exposure nearly doubled the amount of gp120+ epithelial cells in small airway and alveoli cells, suggesting that cigarette smoke promotes HIV replication within epithelial cells or inhibits the clearance of gp120+ epithelial cells.

SHIV increased inflammatory markers beyond the effects of smoking, such as neutrophils and lymphocytes in the lung. Both smoking and SHIV independently and synergistically up-regulated mRNA of MUC5AC, a major airway secretory mucin that serves as marker for airway mucus production and obstructive lung disease. In addition, SHIV infection and smoking increased interleukin-13 expression in airway epithelial cells, which further promoted MUC5AC, and goblet cell metaplasia/hyperplasia. The authors also identified that both smoking and SHIV decreased markers of bronchial epithelial cell tight junctions. Further, physiological evaluation showed that both smoking and SHIV cooperate to induce airflow limitations and structural changes in central airways. Thus, this investigation provides plausible mechanistic insights into how HIV infection silently promotes inflammatory and structural changes in the lungs leading to chronic lung inflammatory disorders. Given multiple possible confounders among patients with these diseases, validation studies are necessary to confirm these results. However, the results presented in this paper support that the lung should not be considered just a silent reservoir of HIV and suggest that the current therapeutic goals of ART might not be sufficient in light of the chronic effects of HIV that we are now starting to understand.

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