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Molecular analysis of viral RNAs in mice persistently infected with lymphocytic choriomeningitis virus
1Department of Immunology, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Abstract:
Infection of newborn mice with lymphocytic choriomeningitis virus (LCMV) results in a lifelong persistent infection. Persistently infected animals continuously produce low levels of infectious virus and accumulate large amounts of intracellular viral nucleic acid (P. J. Southern, P. Blount, and M. B. A. Oldstone, Nature [London] 312:555-558, 1984). We have used gel electrophoresis and hybridization techniques to analyze viral RNAs that appear during the establishment and maintenance of a persistent LCMV infection in vivo to identify any role for defective and/or defective interfering RNAs. We have found a complex, heterogeneously sized population of viral RNAs in multiple independent tissues that is uniquely associated with persistent infections in vivo, but we have not yet established whether these RNAs have a causal or a consequential association with persistent infection by LCMV. Within the complex virus RNA population, full-length genomic L and S RNAs were readily detectable and represented the most abundant individual viral RNA species. RNAs apparently corresponding in size to the viral nucleoprotein and glycoprotein mRNAs could also be detected in these tissue RNA samples. The presence of glycoprotein mRNA indicates a potential mechanism of posttranscriptional regulation to account for the previously documented restriction in viral glycoprotein expression in persistently infected mice (M. B. A. Oldstone and M. J. Buchmeier, Nature (London) 300:360-362, 1982).
Insights
Persistent lymphocytic choriomeningitis virus (LCMV) infection in mice involves unique viral RNA populations. Further research is needed to determine if these RNA changes cause or result from the chronic LCMV infection.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Newborn mice infected with lymphocytic choriomeningitis virus (LCMV) develop lifelong persistent infections.
- Persistently infected animals continuously shed low levels of infectious virus and accumulate significant intracellular viral nucleic acid.
Purpose of the Study:
- To analyze viral RNAs during the establishment and maintenance of persistent LCMV infection in vivo.
- To identify the role of defective and/or defective interfering RNAs in persistent LCMV infection.
Main Methods:
- Gel electrophoresis and hybridization techniques were employed to analyze viral RNAs.
- Analysis was performed on RNA from multiple tissues of persistently infected mice.
Main Results:
- A complex, heterogeneously sized population of viral RNAs was found, uniquely associated with persistent LCMV infections in vivo.
- Full-length genomic L and S RNAs were the most abundant species. RNAs corresponding to nucleoprotein and glycoprotein mRNAs were also detected.
Conclusions:
- The presence of glycoprotein mRNA suggests a posttranscriptional regulation mechanism for restricted viral glycoprotein expression in persistently infected mice.
- The causal or consequential role of the observed complex viral RNA population in persistent LCMV infection remains to be established.