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Ambisense RNA

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Although arenaviruses are considered (−) strand RNA viruses, their genomic RNA is in fact ambisense: mRNAs are produced both from (−) strand genomic RNA and from complementary full-length (+) strands. The arenavirus genome comprises two RNA segments, S (small) and L (large) (Fig. 6.23). Shortly after infection, RdRP that enters with viral particles synthesizes mRNAs from the 3′ region of both RNA segments. Synthesis of each mRNA terminates at a stem-loop structure. These mRNAs, which are translated to produce the nucleocapsid (NP) protein and RdRP (L), respectively, are the only viral RNAs made during the first several hours of infection. Later in infection, the block imposed by the stem-loop structure is overcome, permitting the synthesis of full-length S and L (+) strand RNAs. It was initially thought that melting of the stem-loop structure by the NP protein allowed the transcription termination signal to be bypassed. It now seems more likely that two different configurations of the RNA polymerases are made in infected cells: one for synthesis of mRNA and a second for synthesis of full-length copies of the genome. The finding that viral mRNAs are capped while genomes are not is consistent with this hypothesis.

Principles of Virology

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