Precision mouse models with expanded tropism for human pathogens

Wahl, Angela; De, Chandrav; Fernandez, Maria Abad; Lenarcic, Erik M.; Xu, Yinyan; Cockrell, Adam S.; Cleary, Rachel A.; Johnson, Claire; Schramm, Nathaniel J.; Rank, Laura; Newsome, Isabel G.; Vincent, Heather A.; Sanders, Wes; Aguilera-Sandoval, Christian R.; Boone, Allison; Hildebrand, William H.; Dayton, Paul A.; Baric, Ralph S.; Pickles, Raymond J.; Braunstein, Miriam; Moorman, Nathaniel J.; Goonetilleke, Nilu; García, J. Víctor

doi:10.1038/s41587-019-0225-9

Cited by 79 publications

(117 citation statements)

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“…Many human pathogens show preferential, often exclusive, tropism for human cells and do not replicate in experimental animals. In this issue, Wahl et al 1 provide mouse models to study respiratory pathogens, which are the leading cause of death by infectious disease globally and the fourth most common cause of death overall. The mice carry both human fetal lung tissue and a humanized immune system, allowing the study of pathogen replication in human cells from the respiratory tract and of human immune responses to the pathogens in an animal model.…”

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confidence: 99%

“…Wahl et al 1 build on decades of work on developing immunodeficient mice that allow engraftment of human immune cells and tissues ( Fig. 1).…”

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confidence: 99%

“…All these strains lack mouse T cells, B cells and innate lymphoid cells, including natural killer cells. A frequently used strain, which is also used by Wahl et al 1 , is a non-obese diabetic-severe combined immunodeficiency (NOD-SCID) strain with a Prkdc mutation and an IL2Rγ deficiency, called NSG mice.…”

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confidence: 99%

“…To study pathogens that infect non-hematopoietic cells, researchers can transplant human tissues along with hematopoietic cells. For example, mice engrafted with human immune cells and human hepatocytes (HIS-HuHEP mice) 10 have been used to study immune reactions against human liver trophic viruses like hepatitis B virus 11 Wahl et al 1 show that the grafts support robust replication of clinically relevant human respiratory pathogens that have no or limited tropism to non-human cells. These pathogens-including Middle East respiratory coronavirus, Zika virus, respiratory syncytial virus and HCMVrepresent a risk for human health globally.…”

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confidence: 99%

“…Wahl et al 1 did not investigate whether there is affinity maturation of the HCMVspecific IgGs. If the mice support somatic hypermutation, this would represent an important advance because thus far highaffinity, class-switched, antigen-specific antibodies have rarely been produced in humanized mouse models.…”

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confidence: 99%

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Modeling human lung infections in mice

Spits

Villaudy

2019

Nat Biotechnol

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mentioning

confidence: 99%

“…Wahl et al 1 build on decades of work on developing immunodeficient mice that allow engraftment of human immune cells and tissues ( Fig. 1).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Modeling human lung infections in mice

Spits

Villaudy

2019

Nat Biotechnol

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Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

Hemmi

Spindler

2019

FEBS Letters

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Small laboratory animals are powerful models for investigating in vivo viral pathogenesis of a number of viruses. For adenoviruses (AdVs), however, species-specificity poses limitations to studying human adenoviruses (HAdVs) in mice and other small laboratory animals. Thus, this review covers work on naturally occurring mouse AdVs, primarily mouse adenovirus type 1 (MAdV-1), a member of the species Murine mastadenovirus A. Molecular genetics, virus life cycle, cell and tissue tropism, interactions with the host immune response, persistence, and host genetics of susceptibility are described. A brief discussion of MAdV-2 (member of species Murine mastadenovirus B) and MAdV-3 (member of species Murine mastadenovirus C) is included. We report the use of MAdVs in the development of vectors and vaccines.

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The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin

Segreto

Deigin²

2020

BioEssays

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Severe acute respiratory syndrome‐coronavirus (SARS‐CoV)‐2′s origin is still controversial. Genomic analyses show SARS‐CoV‐2 likely to be chimeric, most of its sequence closest to bat CoV RaTG13, whereas its receptor binding domain (RBD) is almost identical to that of a pangolin CoV. Chimeric viruses can arise via natural recombination or human intervention. The furin cleavage site in the spike protein of SARS‐CoV‐2 confers to the virus the ability to cross species and tissue barriers, but was previously unseen in other SARS‐like CoVs. Might genetic manipulations have been performed in order to evaluate pangolins as possible intermediate hosts for bat‐derived CoVs that were originally unable to bind to human receptors? Both cleavage site and specific RBD could result from site‐directed mutagenesis, a procedure that does not leave a trace. Considering the devastating impact of SARS‐CoV‐2 and importance of preventing future pandemics, researchers have a responsibility to carry out a thorough analysis of all possible SARS‐CoV‐2 origins.

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Precision mouse models with expanded tropism for human pathogens

Cited by 79 publications

References 73 publications

Modeling human lung infections in mice

Modeling human lung infections in mice

Murine adenoviruses: tools for studying adenovirus pathogenesis in a natural host

The genetic structure of SARS‐CoV‐2 does not rule out a laboratory origin

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