The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae

Irina V. Alymova, Allen Portner, Toru Takimoto, Kelli L. Boyd, Y. Sudhakara Babu, Jonathan Mccullers

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

An association exists between respiratory viruses and bacterial infections. Prevention or treatment of the preceding viral infection is a logical goal for reducing this important cause of morbidity and mortality. The ability of the novel, selective parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 to prevent the synergism between a paramyxovirus and Streptococcus pneumoniae was examined in this study. A model of secondary bacterial pneumonia after infection with a recombinant Sendai virus whose hemagglutinin- neuraminidase gene was replaced with that of human parainfluenza virus type 1 [rSV(hHN)] was established in mice. Challenge of mice with a sublethal dose of S. pneumoniae 7 days after a sublethal infection with rSV(hHN) (synergistic group) caused 100% mortality. Bacterial infection preceding viral infection had no effect on survival. The mean bacterial titers in the synergistic group were significantly higher than in mice infected with bacteria only. The virus titers were similar in mice infected with rSV(hHN) alone and in dually infected mice. Intranasal administration of BCX 2798 at 10 mg/kg per day to the synergistic group of mice starting 4 h before virus infection protected 80% of animals from death. This effect was accompanied by a significant reduction in lung viral and bacterial titers. Treatment of mice 24 h after the rSV(hHN) infection showed no protection against synergistic lethality. Together, our results indicate that parainfluenza viruses can prime for secondary bacterial infections. Prophylaxis of parainfluenza virus infections with antivirals might be an effective strategy for prevention of secondary bacterial complications in humans.

Original languageEnglish (US)
Pages (from-to)398-405
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2005

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Paramyxoviridae Infections
Hemagglutinins
Neuraminidase
Streptococcus pneumoniae
Viruses
Virus Diseases
Human parainfluenza virus 1
Bacterial Infections
Infection
Bacterial Pneumonia
Sendai virus
Intranasal Administration
Mortality
Secondary Prevention
4-zido-5-isobutyrylamino-2,3-didehydro-2,3,4,5-tetradeoxyglycerogalacto-2-nonulopyranosic acid
Viral Load
Coinfection
Respiratory Tract Infections
Antiviral Agents
Morbidity

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

The novel parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 prevents lethal synergism between a paramyxovirus and Streptococcus pneumoniae. / Alymova, Irina V.; Portner, Allen; Takimoto, Toru; Boyd, Kelli L.; Babu, Y. Sudhakara; Mccullers, Jonathan.

In: Antimicrobial Agents and Chemotherapy, Vol. 49, No. 1, 01.01.2005, p. 398-405.

Research output: Contribution to journalArticle

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