Uncoding the Cellular Receptor for Lymphocytic Choriomeningitis Virus and Lassa Fever Virus W. Cao, P. Borrow, H. Lewicki, M.B.A. Oldstone Viral infection starts with the specific attachment of the virus to a component of the cell surface. This interaction largely determines the tropism and host range of infection and plays a part in the overall pathogenesis of the virus. It is also the prototype virus for the arenavirus family, which includes Lassa fever virus, a major pathogen in humans. This glycoprotein was biochemically purified from a mouse fibroblast cell line and analyzed with mass spectrometry to determine the internal sequence. Disruption of the gene for -dystroglycan in stem cells ordinarily permissive to LCMV prevented LCMV binding and infection.
Viral persistence is an evasion of the host's immunologic surveillance system.
These CTLs recognized and lysed target cells infected with LCMV or coated with the nucleoprotein peptide but were unable to clear persistent LCMV infection. Other mice persistently infected with LCMV were treated with combinatorial therapy that consisted of the antiviral agent ribavirin and repeated peptide inoculations. However, the level of virus in the serum and organs was not further decreased. Affinity analysis indicated that the CTLs in uninfected peptide-inoculated controls had high affinity for LCMV nucleoprotein, whereas the CTLs in persistently infected mice had low affinity for the protein. These data indicate that in mice persistently infected with virus in utero or at birth, complete tolerance does not occur and antiviral CTLs can be generated.