HIV gp120 induces mucus formation in human bronchial epithelial cells through CXCR4/α7-nicotinic acetylcholine receptors.

TitleHIV gp120 induces mucus formation in human bronchial epithelial cells through CXCR4/α7-nicotinic acetylcholine receptors.
Publication TypeJournal Article
Year of Publication2013
AuthorsGundavarapu, S, Mishra, NC, Singh, SP, Langley, RJ, Saeed, AImran, Feghali-Bostwick, CA, J McIntosh, M, Hutt, J, Hegde, R, Buch, S, Sopori, ML
JournalPLoS One
Date Published2013
Keywordsalpha7 Nicotinic Acetylcholine Receptor, Animals, Antiretroviral Therapy, Highly Active, Bronchi, Epithelial Cells, External, HIV Envelope Protein gp120, HIV Infections, Humans, Macaca mulatta, Mucin 5AC, Mucus, Receptors, CXCR4, Receptors, CXCR5, Receptors, GABA-A, Simian Acquired Immunodeficiency Syndrome

Lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, and lung infections are major causes of morbidity and mortality among HIV-infected patients even in the era of antiretroviral therapy (ART). Many of these diseases are strongly associated with smoking and smoking is more common among HIV-infected than uninfected people; however, HIV is an independent risk factor for chronic bronchitis, COPD, and asthma. The mechanism by which HIV promotes these diseases is unclear. Excessive airway mucus formation is a characteristic of these diseases and contributes to airway obstruction and lung infections. HIV gp120 plays a critical role in several HIV-related pathologies and we investigated whether HIV gp120 promoted airway mucus formation in normal human bronchial epithelial (NHBE) cells. We found that NHBE cells expressed the HIV-coreceptor CXCR4 but not CCR5 and produced mucus in response to CXCR4-tropic gp120. The gp120-induced mucus formation was blocked by the inhibitors of CXCR4, α7-nicotinic acetylcholine receptor (α7-nAChR), and γ-aminobutyric acid (GABA)AR but not the antagonists of CCR5 and epithelial growth factor receptor (EGFR). These results identify two distinct pathways (α7-nAChR-GABAAR and EGFR) for airway mucus formation and demonstrate for the first time that HIV-gp120 induces and regulates mucus formation in the airway epithelial cells through the CXCR4-α7-nAChR-GABAAR pathway. Interestingly, lung sections from HIV ± ART and simian immunodeficiency virus (SIV) ± ART have significantly more mucus and gp120-immunoreactivity than control lung sections from humans and macaques, respectively. Thus, even after ART, lungs from HIV-infected patients contain significant amounts of gp120 and mucus that may contribute to the higher incidence of obstructive pulmonary diseases in this population.

Alternate JournalPLoS ONE
PubMed ID24155926
PubMed Central IDPMC3796539
Grant ListDA024442 / DA / NIDA NIH HHS / United States
GM103801 / GM / NIGMS NIH HHS / United States
GM48677 / GM / NIGMS NIH HHS / United States