Andes Virus Genome Mutations That Are Likely Associated with Animal Model Attenuation and Human Person-to-Person Transmission
Carla M. Bellomo,
Daniel O. Alonso,
Unai Pérez-Sautu,
Karla Prieto,
Sebastian Kehl,
Rocio M. Coelho,
Natalia Periolo,
Nicholas Di Paola,
Natalia Ferressini-Gerpe,
Jens H. Kuhn,
Mariano Sanchez-Lockhart,
Gustavo Palacios,
Valeria P. Martínez
Affiliations
Carla M. Bellomo
Laboratorio Nacional de Referencia de Hantavirus, Instituto Nacional de Enfermedades Infecciosas, Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran, Buenos Aires, Argentina
Daniel O. Alonso
Laboratorio Nacional de Referencia de Hantavirus, Instituto Nacional de Enfermedades Infecciosas, Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran, Buenos Aires, Argentina
Unai Pérez-Sautu
Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Karla Prieto
Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Sebastian Kehl
Laboratorio Nacional de Referencia de Hantavirus, Instituto Nacional de Enfermedades Infecciosas, Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran, Buenos Aires, Argentina
Rocio M. Coelho
Laboratorio Nacional de Referencia de Hantavirus, Instituto Nacional de Enfermedades Infecciosas, Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran, Buenos Aires, Argentina
Natalia Periolo
Laboratorio Nacional de Referencia de Hantavirus, Instituto Nacional de Enfermedades Infecciosas, Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran, Buenos Aires, Argentina
Nicholas Di Paola
Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Natalia Ferressini-Gerpe
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Jens H. Kuhn
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, Maryland, USA
Mariano Sanchez-Lockhart
Center for Genome Sciences, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA
Gustavo Palacios
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
Valeria P. Martínez
Laboratorio Nacional de Referencia de Hantavirus, Instituto Nacional de Enfermedades Infecciosas, Administración Nacional de Laboratorios e Institutos de Salud Dr. Carlos G. Malbran, Buenos Aires, Argentina
ABSTRACT We performed whole-genome sequencing with bait enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo, including early, intermediate, and late cell culture, passages of an ANDV isolate from that animal, and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino acid substitutions related to cell culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Changes in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased virulence in the small-animal model. Finally, we identified three amino acid substitutions, two in the small nonstructural protein and one in the glycoprotein, that were only present in the clade of viruses associated with efficient person-to-person transmission. Our results indicate that there are single-nucleotide polymorphisms that could be used to predict strain-specific ANDV virulence and/or transmissibility. IMPORTANCE Several orthohantaviruses cause the zoonotic disease hantavirus pulmonary syndrome (HPS) in the Americas. Among them, HPS caused by Andes virus (ANDV) is of great public health concern because it is associated with the highest case fatality rate (up to 50%). ANDV is also the only orthohantavirus associated with relatively robust evidence of person-to-person transmission. This work reveals nucleotide changes in the ANDV genome that are associated with virulence attenuation in an animal model and increased transmissibility in humans. These findings may pave the way to early severity predictions in future ANDV-caused HPS outbreaks.
