Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques

Hitendra S. Chand, Rodrigo Vazquez-Guillamet, Christopher Royer, Karin Rudolph, Neerad Mishra, Shashi P. Singh, Shah S. Hussain, Edward Barrett, Shannon Callen, Siddappa Nagadenahalli Byrareddy, Maria Cristina Vazquez Guillamet, Jawad Abukhalaf, Aryaz Sheybani, Vernat Exil, Veena Raizada, Hemant Agarwal, Madhavan Nair, Francois Villinger, Shilpa J Buch, Mohan Sopori

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In the era of combined antiretroviral therapy (cART), lung diseases such as chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) are common among persons living with HIV (PLWH), particularly smokers. Although smoking is highly prevalent among PLWH, HIV may be an independent risk factor for lung diseases; however, the role of HIV and cigarette smoke (CS) and their potential interaction in the development of chronic lung diseases among PLWH has not been delineated. To investigate this interaction, cynomolgus macaques were exposed to CS and/or simian-adapted human immunodeficiency virus (SHIV) and treated with cART. The development of CB and the lung functions were evaluated following CS±SHIV treatment. The results showed that in the lung, SHIV was a strong independent risk factor for goblet cell metaplasia/hyperplasia and mucus formation, MUC5AC synthesis, loss of tight junction proteins, and increased expression of Th2 cytokines/transcription factors. In addition, SHIV and CS synergistically reduced lung function and increased extrathoracic tracheal ring thickness. Interestingly, SHIV infection generated significant numbers of HIV-gp120+ epithelial cells (HGECs) in small airways and alveoli, and their numbers doubled in CS+SHIV-infected lungs. We conclude that even with cART, SHIV independently induces CB and pro-COPD changes in the lung, and the effects are exacerbated by CS.

Original languageEnglish (US)
Pages (from-to)5428-5433
Number of pages6
JournalJournal of Clinical Investigation
Volume128
Issue number12
DOIs
StatePublished - Dec 3 2018

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Macaca
Smoke
Tobacco Products
HIV
Pathology
Lung
Chronic Bronchitis
Lung Diseases
Chronic Obstructive Pulmonary Disease
HIV Envelope Protein gp120
Tight Junction Proteins
Goblet Cells
Metaplasia
Virus Diseases
Mucus
Hyperplasia
Chronic Disease
Transcription Factors
Therapeutics
Smoking

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chand, H. S., Vazquez-Guillamet, R., Royer, C., Rudolph, K., Mishra, N., Singh, S. P., ... Sopori, M. (2018). Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques. Journal of Clinical Investigation, 128(12), 5428-5433. https://doi.org/10.1172/JCI121935

Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques. / Chand, Hitendra S.; Vazquez-Guillamet, Rodrigo; Royer, Christopher; Rudolph, Karin; Mishra, Neerad; Singh, Shashi P.; Hussain, Shah S.; Barrett, Edward; Callen, Shannon; Byrareddy, Siddappa Nagadenahalli; Vazquez Guillamet, Maria Cristina; Abukhalaf, Jawad; Sheybani, Aryaz; Exil, Vernat; Raizada, Veena; Agarwal, Hemant; Nair, Madhavan; Villinger, Francois; Buch, Shilpa J; Sopori, Mohan.

In: Journal of Clinical Investigation, Vol. 128, No. 12, 03.12.2018, p. 5428-5433.

Research output: Contribution to journalArticle

Chand, HS, Vazquez-Guillamet, R, Royer, C, Rudolph, K, Mishra, N, Singh, SP, Hussain, SS, Barrett, E, Callen, S, Byrareddy, SN, Vazquez Guillamet, MC, Abukhalaf, J, Sheybani, A, Exil, V, Raizada, V, Agarwal, H, Nair, M, Villinger, F, Buch, SJ & Sopori, M 2018, 'Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques', Journal of Clinical Investigation, vol. 128, no. 12, pp. 5428-5433. https://doi.org/10.1172/JCI121935
Chand HS, Vazquez-Guillamet R, Royer C, Rudolph K, Mishra N, Singh SP et al. Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques. Journal of Clinical Investigation. 2018 Dec 3;128(12):5428-5433. https://doi.org/10.1172/JCI121935
Chand, Hitendra S. ; Vazquez-Guillamet, Rodrigo ; Royer, Christopher ; Rudolph, Karin ; Mishra, Neerad ; Singh, Shashi P. ; Hussain, Shah S. ; Barrett, Edward ; Callen, Shannon ; Byrareddy, Siddappa Nagadenahalli ; Vazquez Guillamet, Maria Cristina ; Abukhalaf, Jawad ; Sheybani, Aryaz ; Exil, Vernat ; Raizada, Veena ; Agarwal, Hemant ; Nair, Madhavan ; Villinger, Francois ; Buch, Shilpa J ; Sopori, Mohan. / Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques. In: Journal of Clinical Investigation. 2018 ; Vol. 128, No. 12. pp. 5428-5433.
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