Animal Challenge Models of Henipavirus Infection and Pathogenesis

Abstract

The henipaviruses, Hendra virus (HeV), and Nipah virus (NiV), are enigmatic emerging pathogens that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. Amongst people, case fatality rates range between 40 and 75% and there are no vaccines or treatments approved for human use. A number of species of animals including guinea pigs, hamsters, cats, ferrets, pigs, and African green monkeys have been employed as animal models of human henipavirus infection. Here, we review the development of animal models for henipavirus infection, discuss the pathology and pathogenesis of these models, and assess the utility of each model to recapitulate important aspects of henipavirus-mediated disease seen in humans.

Nipah Virus Envelope-Pseudotyped Lentiviruses Efficiently Target ephrinB2-Positive Stem Cell Populations In Vitro and Bypass the Liver Sink When Administered In Vivo

“…CD34 is expressed on human hematopoietic stem and progenitor cells (HSPCs), although only a small fraction of CD34 ϩ cells are true HSCs that have extensive selfrenewal capacity in vitro and can engraft immunodeficient mice (30,44). At an MOI of 1,000, both T5F/wt G and T5F⌬N3/wt G NiVpp reproducibly transduced 3.6% and 3.5% of CD34 ϩ cells, respectively.…”

“…4D). True human HSCs have two cardinal properties: multipotency, defined as the ability to differentiate into all blood cell lineages; and long-term (LT) self-renewal, defined by the inexhaustible ability to produce progeny functionally identical to the parent upon cell division (44). Human HSCs with these properties are enriched in the Lin Ϫ…”

Paramyxovirus evasion of innate immunity: Diverse strategies for common targets

“…While in vitro infection approaches are clearly closer to natural infection than transfection, they also use controlled in vitro conditions including the inoculation of cultured monolayers of specific cell types with precise multiplicities of infection, and treatments with specific concentrations of IFNs. By contrast, in natural infection the kinetics of viral protein expression and induction of the IFN system is highly dynamic, involving both infected cells and professional IFN-producing cells, and factors such as the infectious dose, route of infection, host species, and infectious spread to specific tissues can vary greatly, significantly affecting requirements for IFN antagonism and the disease outcome [128] . Thus, the diverse mechanisms of IFN antagonism identified in transfection studies may have vital roles in infection in vivo.…”

Efficient Reverse Genetics Reveals Genetic Determinants of Budding and Fusogenic Differences between Nipah and Hendra Viruses and Enables Real-Time Monitoring of Viral Spread in Small Animal Models of Henipavirus Infection

“…Although NiV and HeV present grossly similar outcomes in human cases and established animal models (13,16,17), the few studies that have directly compared NiV and HeV replication and pathogenesis in vitro and in vivo have shown significant but variable differences (18)(19)(20) depending on the animal model used.…”