A single-amino acid difference between rodent and human Andes virus affects viral glycoprotein trafficking

Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), with rare outbreaks involving person-to-person transmission. A human ANDV isolate from one such outbreak and a rodent isolate from the same region differ in lethality in Syrian golden hamsters. Genomic analysis revealed 25 nonsynonymous substitutions, including one leading to a T641I change in the human ANDV glycoprotein precursor near its cleavage site. Although the isolates differed in growth kinetics, strand-specific RT-qPCR did not support major differences in viral RNA synthesis, whereas virion release was delayed in the case of the human isolate. In human cell expression systems, a single I641T substitution in the human ANDV glycoprotein resulted in decreased Golgi retention and faster release of virion-like particles relative to wild-type glycoprotein. Since ANDV egress takes place at the Golgi, the T641I change present in the human ANDV isolate may represent a human adaptive mutation influencing glycoprotein trafficking and virus particle release.