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The primary structure of the lymphocytic choriomeningitis virus L gene encodes a putative RNA polymerase
M Salvato1, E Shimomaye, M B Oldstone
1Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
Abstract:
The complete RNA sequence of the L protein gene of lymphocytic choriomeningitis virus (LCMV) is presented. It is the first L protein sequence to be obtained for the Arenaviridae, a family of single-stranded RNA viruses which includes Lassa fever virus, and the Tacaribe complex viruses such as Pichinde and the Argentine and Bolivian hemorrhagic fever viruses. It is the largest open reading frame on the L RNA spanning 6633 nucleotides and coding for a 2210 amino acid protein with a calculated molecular weight of 254,529. Antipeptide sera identify a gene product encoded on the L RNA: it has a mass of approximately 200,000 Da and is found in virions and ribonucleoprotein complexes from infected cells (M. Singh, F. Fuller-Pace, M. J. Buchmeier, and P. J. Southern, 1987, Virology, 161, 448-456). Mutations mapped to the L gene affect plaque morphology (Kirk et al., 1980), the lethality of a virulent LCMV strain on guinea pigs (Y. Riviere, R. Ahmed, P. J. Southern, M. J. Buchmeier, and M. B. A. Oldstone, 1985, J. Virol., 55, 704-709), and the ability of a variant strain of LCMV to suppress the cytotoxic T-cell response and initiate persistent infection (M. Salvato, E. Shimomaye, P. Southern, and M. B. A. Oldstone, 1988, Virology, 164, 517-522; Ahmed et al., 1988). All of these phenotypes indicate that the viral genes on the L strand are critical elements controlling virus replication and the pattern of LCMV infection. The L gene sequence encodes a viral polymerase although this protein bears little resemblance to the published sequences of other RNA virus polymerases. Therefore the LCMV polymerase likely represents a distinct category of viral transcriptase.
Insights
This study presents the first complete RNA sequence for the L protein gene of lymphocytic choriomeningitis virus (LCMV), a crucial component for viral replication and infection patterns. The LCMV polymerase encoded by this gene represents a distinct category of viral transcriptase.
Area of Science:
- Virology
- Molecular Biology
- Genomics
Background:
- Lymphocytic choriomeningitis virus (LCMV) belongs to the Arenaviridae family, which includes significant human pathogens like Lassa fever virus.
- The L protein gene is critical for viral replication and pathogenesis, influencing plaque morphology, lethality, and immune response modulation.
- Previous understanding of the LCMV L protein and its encoded polymerase function was limited.
Purpose of the Study:
- To determine and present the complete RNA sequence of the L protein gene of LCMV.
- To characterize the L protein as the first obtained sequence for the Arenaviridae family.
- To investigate the functional implications of the L gene in LCMV replication and infection.
Main Methods:
- RNA sequencing to obtain the complete L gene sequence.
- Bioinformatic analysis to identify the largest open reading frame and predict protein characteristics.
- Antipeptide sera were used to identify the gene product in infected cells and virions.
Main Results:
- The complete RNA sequence of the LCMV L protein gene was determined, spanning 6633 nucleotides.
- This gene codes for a 2210 amino acid protein (molecular weight 254,529 Da), identified as the viral polymerase.
- The identified L protein product (approx. 200,000 Da) was detected in virions and infected cell complexes.
- Mutations in the L gene were linked to significant phenotypic changes, including altered plaque morphology, virulence, and immune suppression.
Conclusions:
- The LCMV L gene sequence provides critical insights into viral replication and pathogenesis.
- The encoded viral polymerase shows limited homology to other known RNA virus polymerases, suggesting a unique category of viral transcriptase.
- This foundational sequence data is essential for understanding Arenaviridae biology and developing antiviral strategies.