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1.
Emerg Microbes Infect ; 12(1): 2212809, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37191590

RESUMO

Influenza A viruses (IAV) cause annual epidemics and occasional pandemics in humans. The most recent pandemic outbreak occurred in 2009 with H1N1pdm09. This virus, which most likely reassorted in swine before its transmission to humans, was reintroduced into the swine population and continues circulating ever since. In order to assess its potential to cause reassortants on a cellular level, human origin H1N1pdm09 and a recent Eurasian avian-like H1N1 swine IAV were (co-)passaged in the newly generated swine lung cell line C22. Co-infection with both viruses gave rise to numerous reassortants that additionally carry different mutations which can partially be found in nature as well. Reassortment most frequently affected the PB1, PA and NA segments with the swine IAV as recipient. These reassortants reached higher titers in swine lung cells and were able to replicate in genuine human lung tissue explants ex vivo, suggesting a possible zoonotic potential. Interestingly, reassortment and mutations in the viral ribonucleoprotein complex influence the viral polymerase activity in a cell type and species-specific manner. In summary, we demonstrate reassortment promiscuity of these viruses in a novel swine lung cell model and indicate a possible zoonotic potential of the reassortants.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A , Influenza Humana , Infecções por Orthomyxoviridae , Doenças dos Suínos , Animais , Humanos , Suínos , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/veterinária , Vírus da Influenza A Subtipo H1N1/genética , Vírus Reordenados/genética , Vírus da Influenza A/genética , Genômica , Doenças dos Suínos/epidemiologia , Influenza Humana/epidemiologia
2.
Evol Med Public Health ; 9(1): 383-392, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925844

RESUMO

Research in infection biology aims to understand the complex nature of host-pathogen interactions. While this knowledge facilitates strategies for preventing and treating diseases, it can also be intentionally misused to cause harm. Such dual-use risk is potentially high for highly pathogenic microbes such as Risk Group-3 (RG3) bacteria and RG4 viruses, which could be used in bioterrorism attacks. However, other pathogens such as influenza virus (IV) and enterohemorrhagic Escherichia coli (EHEC), usually classified as RG2 pathogens, also demonstrate high dual-use risk. As the currently approved therapeutics against these pathogens are not satisfactorily effective, previous outbreaks of these pathogens caused enormous public fear, media attention and economic burden. In this interdisciplinary review, we summarize the current perspectives of dual-use research on IV and EHEC, and further highlight the dual-use risk associated with evolutionary experiments with these infectious pathogens. We support the need to carry out experiments pertaining to pathogen evolution, including to gain predictive insights on their evolutionary trajectories, which cannot be otherwise achieved with stand-alone theoretical models and epidemiological data. However, we also advocate for increased awareness and assessment strategies to better quantify the risks-versus-benefits associated with such evolutionary experiments. In addition to building public trust in dual-use research, we propose that these approaches can be extended to other pathogens currently classified as low risk, but bearing high dual-use potential, given the particular pressing nature of their rapid evolutionary potential.

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