Cells of the human respiratory tract support the replication of pathogenic Old World orthohantavirus Puumala

Transmission of all known pathogenic orthohantaviruses (family Hantaviridae) usually occurs via inhalation of aerosols contaminated with viral particles derived from infected rodents and organ manifestation of infections is characterized by lung and kidney involvement. Orthohantaviruses found in Eur...

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Bibliographic Details
Published in:	Virology journal 2021-08, Vol.18 (1), p.169-169, Article 169
Main Authors:	Hägele, Stefan, Nusshag, Christian, Müller, Alexander, Baumann, Alexandra, Zeier, Martin, Krautkrämer, Ellen
Format:	Article
Language:	eng
Subjects:	Antibodies Antigens Bronchus Care and treatment Cytokeratin Development and progression Endothelial cells Endothelial Cells - virology Endothelium Epithelial cells Epithelium Experiments Flow cytometry Hantavirus Hantaviruses Health aspects Hemorrhage Hemorrhagic Fever with Renal Syndrome Host-virus relationships Humans Infections Infectious diseases Infrared imaging systems Inhalation Integrin Integrins Kidneys Lung Microvasculature Orthohantavirus Primary Cell Culture Proteins Puumala virus Puumala virus - physiology Replication Respiratory System - cytology Respiratory System - virology Respiratory tract diseases Respiratory tract infections Viral infections Virus Replication Viruses
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Summary:	Transmission of all known pathogenic orthohantaviruses (family Hantaviridae) usually occurs via inhalation of aerosols contaminated with viral particles derived from infected rodents and organ manifestation of infections is characterized by lung and kidney involvement. Orthohantaviruses found in Eurasia cause hemorrhagic fever with renal syndrome (HFRS) and New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS). However, cases of infection with Old World orthohantaviruses with severe pulmonary manifestations have also been observed. Therefore, human airway cells may represent initial targets for orthohantavirus infection and may also play a role in the pathogenesis of infections with Eurasian orthohantaviruses. We analyzed the permissiveness of primary endothelial cells of the human pulmonary microvasculature and of primary human epithelial cells derived from bronchi, bronchioles and alveoli for Old World orthohantavirus Puumala virus (PUUV) in vitro. In addition, we examined the expression of orthohantaviral receptors in these cell types. To minimize donor-specific effects, cells from two different donors were tested for each cell type. Productive infection with PUUV was observed for endothelial cells of the microvasculature and for the three tested epithelial cell types derived from different sites of the respiratory tract. Interestingly, infection and particle release were also detected in bronchial and bronchiolar epithelial cells although expression of the orthohantaviral receptor integrin β was not detectable in these cell types. In addition, replication kinetics and viral release demonstrate enormous donor-specific variations. The human respiratory epithelium is among the first targets of orthohantaviral infection and may contribute to virus replication, dissemination and pathogenesis of HFRS-causing orthohantaviruses. Differences in initial pulmonary infection due to donor-specific factors may play a role in the observed broad variance of severity and symptoms of orthohantavirus disease in patients. The absence of detectable levels of integrin α β surface expression on bronchial and small airway epithelial cells indicates an alternate mode of orthohantaviral entry in these cells that is independent from integrin β .
ISSN:	1743-422X 1743-422X