Respiratory syncytial virus-induced chemokine production: linking viral replication to chemokine production in vitro and in vivo

J Infect Dis. 2004 Apr 15;189(8):1419-30. doi: 10.1086/382958. Epub 2004 Apr 2.

Abstract

Respiratory syncytial virus (RSV) is a negative-sense, single-strand RNA virus that can initiate severe bronchiolitis in infants, as well as in elderly adults. Although RSV preferentially infects and replicates in the airway epithelium, studies have shown that RSV has the ability to infect and, to a limited extent, replicate in alveolar macrophages. In the present study, we sought to characterize the RSV-induced chemokine production in vitro and in vivo, because chemokines have been shown to contribute to both the inflammation and pathophysiology of disease. Our results show that RSV-infected airway epithelial cells and alveolar macrophages display differential profiles of chemokine production: airway epithelial cells produce CCL2/monocyte chemoattractant protein-1, CCL5/RANTES, CXCL10/gamma interferon inducible protein-10, and kerotinocyte cytokine (KC); and alveolar macrophages up-regulate CCL5 and macrophage inflammatory protein (MIP)-2 after RSV infection. In vivo, we observed the induction of CCL2, CCL3/MIP-1 alpha, CCL5, CXCL10, and KC after RSV infection. In the present study, we also addressed the necessity for viral infection and/or replication in chemokine induction by use of ultraviolet (UV)-inactivated RSV, as well as RSV inhibitors of binding/infection and replication, that is, NMSO3, a sulfated sialyl lipid compound, and ribavirin, respectively. Our results suggest that viral replication is necessary for optimal chemokine production.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Chemokines / biosynthesis*
  • Chemokines / genetics
  • Chemokines / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells
  • Humans
  • Lipids / pharmacology
  • Lung / virology
  • Macrophages, Alveolar / virology
  • Mice
  • Mice, Inbred BALB C
  • N-Acetylneuraminic Acid / analogs & derivatives*
  • N-Acetylneuraminic Acid / pharmacology
  • Polymerase Chain Reaction
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus, Human / physiology*
  • Ribavirin / pharmacology
  • Up-Regulation
  • Virion / immunology
  • Virus Replication / drug effects
  • Virus Replication / immunology*

Substances

  • (2,2-bis(docosyloxymethyl)propyl-5-acetamido-3,5-dideoxy-4,7,8,9-tetra-O-(sodium oxysulfonyl)glycero-alpha-galacto-2-nonulopyranosid)onate
  • Antiviral Agents
  • Chemokines
  • Lipids
  • RNA, Viral
  • Ribavirin
  • N-Acetylneuraminic Acid