Distinct Biological and Epidemiological Features of Old World and New World Arenaviruses

The Arenaviridae family comprises a diverse group of enveloped, bisegmented, negative-sense RNA viruses that establish persistent infections in rodent hosts and occasionally transmit zoonotically to humans [1-2]. Arenavirus infections range from mild febrile illness to severe hemorrhagic fever with high mortality. Based on geographic distribution, genetic relationships, and antigenic properties, arenaviruses are classified into Old World (OW) and New World (NW) groups. Although recent genomic studies have refined taxonomic placement within the Bunyavirales order [1, 3–5], the OW/NW distinction remains epidemiologically and clinically relevant. Arenaviruses possess an ambisense, bisegmented genome consisting of a small (S) segment (~3.5 kb) encoding the nucleoprotein (NP) and glycoprotein precursor (GPC), and a large (L) segment (~7.2 kb) encoding the RNA-dependent RNA polymerase (L) and the matrix zinc-binding protein (Z) [6–8]. The GPC is cleaved by the host site-1 protease (S1P) into GP1 and GP2, forming the surface glycoprotein complex responsible for receptor binding and membrane fusion [9]. Virions are pleomorphic, 60–300 nm in diameter, and display a characteristic “sandy” appearance on electron microscopy due to incorporated host ribosomes, hence the name arena (Latin for sand) [1,6,10].