The Andes Hantavirus NSs Protein Is Expressed from the Viral Small mRNA by a Leaky Scanning Mechanism

In 4 out of 5 genera in the Bunyaviridae, the smRNA encodes an additional nonstructural protein denominated NSs. In this study, we show that Andes hantavirus (ANDV) SmRNA encodes an NSs protein. Data show that the NSs protein is expressed in the context of an ANDV infection. Ad-ditionally, our results suggest that translation initiation from the NSs initiation codon is mediated by ribosomal subunits that have bypassed the upstreamN protein initiation codon through a leaky scanning mechanism. The Andes virus (ANDV), a rodent-borne hantavirus memberof the Bunyaviridae family of viruses, is the major etiological agent of hantavirus cardiopulmonary syndrome (HCPS) in South America (34). Like all Bunyaviridae members, ANDV features a tripartite genome consisting of three different negative-polarity single-stranded RNA segments, designated large (L), medium (M), and small (S), packed into helical nucleocapsids (18, 36). The L andM segments encode the RNA polymerase and a glycopro-tein precursor that is cotranslationally processed to yield two envelope glycoproteins (Gc and Gn). The small mRNA (SmRNA) of all hantaviruses, including ANDV, encodes th