Recapitulation of treatment response patterns in a novel humanized mouse model for chronic hepatitis B virus infection

Winer, Benjamin Y.; Huang, Tiffany; Low, Benjamin E.; Avery, Cindy; Pais, Mihai-Alexandru; Hrebikova, Gabriela; Siu, Evelyn; Chiriboga, Luis; Wiles, Michael V.; Ploß, Alexander

doi:10.1016/j.virol.2016.12.017

Cited by 17 publications

(12 citation statements)

References 59 publications

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“…Levels of human albumin in mouse serum were quantified by ELISA as described previously (de Jong et al, 2014; Winer et al, 2017); 96-well flat-bottomed plates (Nunc, Thermo Fisher Scientific, Witham MA) were coated with goat anti-human albumin antibody (1:500, Bethel) in coating buffer (1.59g Na 2 CO 3 , 2.93g NaHCO 3 , 1L dH 2 O, pH = 9.6) for 1 hour at 37°C. The plates were washed four times with wash buffer (0.05% Tween 20 (Sigma Aldrich, St. Luis MO) in 1x PBS) then incubated with superblock buffer (Fisher Scientific, Hampton NH) for 1 hour at 37°C.…”

Section: Methodsmentioning

confidence: 99%

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Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice

Dragovic

Agunbiade

Freudzon

et al. 2018

Cell Host & Microbe

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SUMMARY Plasmodium infection begins with the bite of an anopheline mosquito, when sporozoites along with saliva are injected into a vertebrate host. The role of the host responses to mosquito saliva components in malaria remains unclear. We observed that antisera against Anopheles gambiae salivary glands partially protected mice from mosquito-borne Plasmodium infection. Specifically, antibodies to A. gambiae TRIO (AgTRIO), a mosquito salivary gland antigen, contributed to the protection. Mice administered AgTRIO antiserum showed lower Plasmodium liver burden and decreased parasitemia when exposed to infected mosquitoes. Active immunization with AgTRIO was also partially protective against Plasmodium berghei infection. A combination of AgTRIO antiserum and antibodies against Plasmodium circumsporozoite protein, a vaccine candidate, further decreased P. berghei infection. In humanized mice, AgTRIO antiserum afforded some protection against mosquito-transmitted Plasmodium falciparum. AgTRIO antiserum reduced the movement of sporozoites in the murine dermis. AgTRIO may serve as an arthropod-based target against Plasmodium to combat malaria.

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Section: Methodsmentioning

confidence: 99%

“…The transmission of P. falciparum was studied using a humanized mouse model (de Jong et al, 2014; Morosan et al, 2006; Sacci et al, 2006; VanBuskirk et al, 2009; Vaughan et al, 2012; Winer et al, 2017). Our goal was to determine whether AgTRIO antibodies affect mosquito-borne P. falciparum infection.…”

Section: Methodsmentioning

confidence: 99%

Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice

Dragovic

Agunbiade

Freudzon

et al. 2018

Cell Host & Microbe

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“…Subsequently, similar results have been obtained in a variety of liver injury models [74,132,133], including the above mentioned Alb-uPA [73,75] mice as well as fumarylacetoacetate hydrolase knockouts (FAH −/− mice) [76,124], mice expressing a fusion protein of the FK506 binding protein and caspase 8 under control of the albumin promoter (AFC8 mice) [74], mice expressing uPA under the promoter for major urinary protein (MUP-uPA mice) [135], and mice expressing herpes simplex virus thymidine kinase (HSV-TK) [136]. These human-liver chimeric mice support infection with a variety of hepatotropic pathogens, including HBV, HCV, HDV, and most recently HEV [73,76,124,[137][138][139][140][141][142][143]. These mice have been used to study innate host responses to many hepatitis viruses, including HCV, and for testing the efficacy of novel therapeutic regimens; however, the highly immunocompromised status of these human-liver chimeric mice precludes the study of immune-mediated pathogenesis by HCV.…”

Section: Humanized Xenotranslation Models: Human Liver and Immune Celmentioning

confidence: 99%

Animal Models Used in Hepatitis C Virus Research

Berggren

Suzuki

Ploß

2020

IJMS

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The narrow range of species permissive to infection by hepatitis C virus (HCV) presents a unique challenge to the development of useful animal models for studying HCV, as well as host immune responses and development of chronic infection and disease. Following earlier studies in chimpanzees, several unique approaches have been pursued to develop useful animal models for research while avoiding the important ethical concerns and costs inherent in research with chimpanzees. Genetically related hepatotropic viruses that infect animals are being used as surrogates for HCV in research studies; chimeras of these surrogate viruses harboring specific regions of the HCV genome are being developed to improve their utility for vaccine testing. Concurrently, genetically humanized mice are being developed and continually advanced using human factors known to be involved in virus entry and replication. Further, xenotransplantation of human hepatocytes into mice allows for the direct study of HCV infection in human liver tissue in a small animal model. The current advances in each of these approaches are discussed in the present review.

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“…FNRG mice were generated and transplanted as previously described. (7,20) Female mice between 6-10 weeks of age were injected with 1.0 × 10 6 cryopreserved adult human or squirrel monkey hepatocytes. Primary human hepatocytes were obtained from BioIVT (Westbury, NY).…”

Section: Engraftment Of Adult Squirrel Monkey and Human Hepatocytes Imentioning

confidence: 99%

Woolly Monkey–HBV Infection in Squirrel Monkeys as a Surrogate Nonhuman Primate Model of HBV Infection

et al. 2020

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Development of curative therapies for chronic hepatitis B virus (HBV) infection will likely require new animal models. Here, we evaluate HBV infection in squirrel monkeys based on the high‐sequence homology of the HBV receptor, Na+/taurocholate co‐transporting peptide (NTCP), between humans and squirrel monkeys. HBV PreS1 peptide was examined for binding human and squirrel monkey NTCP. Immunodeficient Fah−/−, NOD, Rag1−/−, Il2Rgnull (FNRG) mice engrafted with human or squirrel monkey hepatocytes were challenged with HBV or Woolly Monkey HBV (WMHBV). In addition, adult squirrel monkeys were inoculated with HBV, WMHBV, adeno‐associated virus containing an infectious genome of HBV (AAV‐HBV), and AAV‐WMHBV. Finally, neonate squirrel monkeys were assessed for the potential of chronic infection with WMHBV. PreS1 peptide efficiently bound to human and squirrel monkey NTCP but not to mouse or capuchin NTCP. FNRG mice engrafted with squirrel monkey hepatocytes were susceptible to infection by WMHBV but not human HBV. Similarly, adult squirrel monkeys could be infected with WMHBV but not human HBV, whereas chimeric mice engrafted with human hepatocytes were susceptible to HBV but not WMHBV. Infection of squirrel monkeys with AAV‐WMHBV yielded maximum viremia of 108 genomes/mL with detectable virus for up to 8 months. Notably, covalently closed circular DNA was detected in the liver of these animals. Infection of neonates with WMHBV led to detectable viremia for up to 6 months. Conclusions: Adult and neonate squirrel monkeys exhibited prolonged WMHBV viremia lasting 6‐8 months. This is greater than twice the duration of viremia achieved in other nonhuman primates and suggests that squirrel monkeys may be a suitable model for testing HBV therapeutics.

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Recapitulation of treatment response patterns in a novel humanized mouse model for chronic hepatitis B virus infection

Cited by 17 publications

References 59 publications

Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice

Immunization with AgTRIO, a Protein in Anopheles Saliva, Contributes to Protection against Plasmodium Infection in Mice

Animal Models Used in Hepatitis C Virus Research

Woolly Monkey–HBV Infection in Squirrel Monkeys as a Surrogate Nonhuman Primate Model of HBV Infection

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