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.
Authors
- Adolfo Garcı́a-Sastre (ORCID: https://orcid.org/0000-0002-6551-1827)
- Carla Bellomo (ORCID: https://orcid.org/0000-0001-6869-1707)
- Santiago Vidal (ORCID: https://orcid.org/0000-0002-0105-4583)
- Jens H. Kuhn (ORCID: https://orcid.org/0000-0002-7800-6045)
- Connie S. Schmaljohn (ORCID: https://orcid.org/0000-0001-8852-5482)
- N.M. Ferressini Gerpe (ORCID: https://orcid.org/0000-0003-1210-3085)
- André Filipe Pastor (ORCID: https://orcid.org/0000-0002-5133-9616)
- Mariano Sánchez-Lockhart (ORCID: https://orcid.org/0000-0001-8009-7540)
- Nicole D. Tischler (ORCID: https://orcid.org/0000-0002-4578-4780)
- Maya Tagliavia (ORCID: https://orcid.org/0009-0007-4415-8116)
- Juan Ángel Patin͂o-Galindo (ORCID: https://orcid.org/0000-0002-6832-7179)
- Elaina Giannetti
- Valeria P. Martínez (ORCID: https://orcid.org/0000-0002-4356-8136)
- Maria E. Kaczmarek (ORCID: https://orcid.org/0000-0003-3593-9053)
- Florian Krammer (ORCID: https://orcid.org/0000-0003-4121-776X)
- Gabriella Worwa (ORCID: https://orcid.org/0000-0001-7485-2204)
- Ignacio Mena (ORCID: https://orcid.org/0000-0001-5464-7086)
- Gustavo F. Palacios (ORCID: https://orcid.org/0000-0001-5062-1938)
- Jayden Zhang (ORCID: https://orcid.org/0009-0008-4086-6032)
- Shruti Shirsathe (ORCID: https://orcid.org/0000-0001-7556-233X)
- Rachel Somavarapu (ORCID: https://orcid.org/0000-0001-6016-4021)
Institutions
- United States Army Medical Research Institute of Infectious Diseases (US)
- Universidad San Sebastián (CL)
- Fundación Ciencia and Vida (CL)
- Administración Nacional de Laboratorios e Institutos de Salud (AR)
- National Institute of Allergy and Infectious Diseases (US)
- Tisch Cancer Institute (US)
- Tonix Pharmaceuticals (United States) (US)
- Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness (AT)
- Medical University of Vienna (AT)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-11-06
- DOI
- https://doi.org/10.1126/sciadv.aek2522
- Primary Topic
- Viral Infections and Vectors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agencia Nacional de Investigación y Desarrollo
- Advanced Research Projects Agency
- National Institute of Allergy and Infectious Diseases