Cigarette smoke promotes HIV infection of primary bronchial epithelium and additively suppresses CFTR function

Sci Rep. 2018 May 22;8(1):7984. doi: 10.1038/s41598-018-26095-z.

Abstract

Recurrent lung infections are a common cause of morbidity and mortality in people living with HIV and this is exacerbated in smokers even when administered combination antiretroviral therapy (cART). The incidence of pneumonia is increased with smoking and treatment interruption and is directly dependent on viral load in patients when adjusted for CD4 counts. CFTR dysfunction plays an important role in aberrant airway innate immunity as it is pivotal in regulating mucociliary clearance (MCC) rates and other antibacterial mechanisms of the airway. In our earlier work, we have demonstrated that bronchial epithelium expresses canonical HIV receptors CD4, CCR5 and CXCR4 and can be infected with HIV. HIV Tat suppresses CFTR mRNA and function via TGF-β signaling. In the present study, we demonstrate that cigarette smoke (CS) potentiates HIV infection of bronchial epithelial cells by upregulating CD4 and CCR5 expression. HIV and CS individually and additively suppress CFTR biogenesis and function, possibly explaining the increased incidence of lung infections in HIV patients and its exacerbation in HIV smokers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Cells, Cultured
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology
  • Disease Progression
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial Cells / virology*
  • Gene Expression Regulation / drug effects
  • HIV Infections / genetics
  • HIV Infections / metabolism
  • HIV Infections / pathology*
  • HIV Infections / virology
  • Humans
  • Mucociliary Clearance / drug effects
  • Mucociliary Clearance / genetics
  • Nicotiana* / adverse effects
  • Primary Cell Culture
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / virology*
  • Smoke / adverse effects*
  • Smoking / adverse effects
  • Viral Load / drug effects
  • Viral Load / genetics

Substances

  • CFTR protein, human
  • Smoke
  • Cystic Fibrosis Transmembrane Conductance Regulator