Ribavirin, human convalescent plasma and anti-beta3 integrin antibody inhibit infection by Sin Nombre virus in the deer mouse model

J Gen Virol. 2007 Feb;88(Pt 2):493-505. doi: 10.1099/vir.0.82459-0.

Abstract

The New World hantavirus Sin Nombre virus (SNV) is an aetiological agent for the often-fatal hantavirus cardiopulmonary syndrome (HCPS). There is no disease model for SNV and specific treatments for HCPS do not exist. By using the deer mouse infectious model, the in vivo inhibitory potential of ribavirin, human anti-SNV immune plasma (HIP), an anti-beta3 antibody (ReoPro) and a polyclonal rabbit anti-recombinant nucleocapsid (N) antibody against SNV was investigated. Concurrent intraperitoneal administration of 100 mg ribavirin kg(-1) prevented seroconversion in all mice at day 15 post-inoculation (p.i.). No evidence of infection was detectable by immunohistochemical staining or by quantitative RT-PCR in two of these six mice. Lower doses of ribavirin, between 5 and 50 mg kg(-1), were much less effective at inhibiting infection. Mice given 200 microl aliquots of dilutions as high as 1 : 20 of HIP (neutralizing-antibody titre 800) failed to seroconvert by day 15 p.i. SNV N antigen staining and viral S genome were undetectable in these mice. A subset of mice given higher dilutions of HIP became infected. Treatment with 6 mg ReoPro kg(-1) did not prevent seroconversion, but was able to reduce viral load. Mice treated with 200 microl anti-N antibody or negative human plasma seroconverted when challenged with SNV, and antigen staining and viral loads were comparable to those seen in untreated controls. These results show that ReoPro can lower viral loads and that ribavirin and HIP, but not anti-N antibody, inhibit seroconversion and reduce viral loads in a dose-dependent manner.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Abciximab
  • Animals
  • Antibodies / immunology
  • Antibodies / therapeutic use
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Disease Models, Animal*
  • Hantavirus Pulmonary Syndrome / drug therapy*
  • Hantavirus Pulmonary Syndrome / immunology
  • Hantavirus Pulmonary Syndrome / virology
  • Humans
  • Immune Sera / administration & dosage*
  • Immunoglobulin Fab Fragments / administration & dosage
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Integrin beta3 / immunology
  • Peromyscus
  • Rabbits
  • Ribavirin / administration & dosage
  • Ribavirin / therapeutic use*
  • Sin Nombre virus / pathogenicity*
  • Treatment Outcome

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Antiviral Agents
  • Immune Sera
  • Immunoglobulin Fab Fragments
  • Integrin beta3
  • Ribavirin
  • Abciximab