Arenavirus, molecular genomics

MARIO E. LOZANO

Campos do Jordão, São Paulo, Brasil

Congreso; XVII Encontro Nacional de Virología; 2006

Sociedad Brasilera de Virología

Arenaviridae is a family composed of a growing number of enveloped, single stranded RNA viruses with at least 18 recognized members around the world. All members of the family Arenaviridae were subdivided into two groups based on geographical site of isolation, serological crossreactivities and genetic data. The prototype of the family, lymphocytic choriomeningitis (LCM) virus, is the only member with a worldwide distribution, whilst all other described arenaviruses are known to belong to a restricted geographical area. LCM is a member of the Old World arenavirus group, which also includes Ippy, Lassa, Mobala and Mopeia viruses. The New World arenavirus group, comprises Amapari, Flexal, Guanarito, Junín, Latino, Machupo, Paraná, Pichindé, Tacaribe and Tamiami viruses. In the last decades, new members of the New World group were recognized, Sabiá in Brazil, Oliveros and Pampa in Argentina and Whitewater Arroyo in USA. All arenaviruses, except Tacaribe, have a rodent host, and Lassa, Machupo, Junín, Guanarito, Sabiá and, more recently Whitewater Arroyo, are known to be highly pathogenic for humans. In particular, the South American viruses produce hemorrhagic fevers called Argentine, Bolivian and Venezuelan hemorrhagic fever, respectively, three endemoepidemic diseases with cardiovascular, renal, immunological and neurological alterations. All arenaviruses share morphological and biochemical properties. They are enveloped and their genomes consist of two single-stranded RNA species, designated L (for large, ca. 7 kb) and S (for small, ca. 3,5 kb). The open reading frames of the two RNA species are arranged in opposite orientations (ambisense) and separated by a non-coding intergenic region that is able to form a stable secondary structure. Furthermore, all arenaviruses that were sequenced share a 19 nucleotide long sequence at 3? end of their S RNAs. The L RNA codes for two polypeptides: the RNA polymerase (L) and a small zinc finger-like protein (Z). The S RNA species codes for the nucleocapsid protein, N, and the precursor of the envelope glycoproteins, GPC. N and L are translated from anti-genome-sense mRNAs, complementary to the 3? portion of the viral S or L RNA, respectively. The GPC and Z proteins are translated from viral or genome-sense mRNAs corresponding to the 5? region of the viral S or L RNA, respectively. Proteolytic cleavage of GPC in infected cells produces a signal peptide and the G1 and G2 polypeptides. Both RNA species follow the same transcription strategy. In this sense, the genomic S RNA is transcribed to only two antigenomic forms: the 1.8 kb N mRNA and the 3.4 kb full length S RNA. The antigenomic S RNA serves as the replicative form of the virus and also as the template for GPC mRNA transcription. When translation is inhibited, transcription of the genomic S RNA yields only the N mRNA. This implies that the synthesis of a full length antigenomic copy of S RNA requires an antiterminator. Interestingly, this regulatory function appear to be supplied by the structural N protein.