title: Bioluminescent imaging of vaccinia virus infection in immunocompetent and immunodeficient rats as a model for human smallpox.
abstract: Due to the increasing concern of using smallpox virus as biological weapons for terrorist attack, there is renewed interest in studying the pathogenesis of human smallpox and development of new therapies. Animal models are highly demanded for efficacy and safety examination of new vaccines and therapeutic drugs. Here, we demonstrated that both wild type and immunodeficient rats infected with an engineered vaccinia virus carrying Firefly luciferase reporter gene (rTV-Fluc) could recapitulate infectious and clinical features of human smallpox. Vaccinia viral infection in wild type Sprague-Dawley (SD) rats displayed a diffusible pattern in various organs, including liver, head and limbs. The intensity of bioluminescence generated from rTV-Fluc correlated well with viral loads in tissues. Moreover, neutralizing antibodies had a protective effect against virus reinfection. The recombination activating gene 2 (Rag2) knockout rats generated by transcription activator-like effector nucleases (TALENs) technology were further used to examine the infectivity of the rTV-Fluc in immunodeficient populations. Here we demonstrated that Rag2-/- rats were more susceptible to rTV-Fluc than SD rats with a slower virus clearance rate. Therefore, the rTV-Fluc/SD rats and rTV-Fluc/Rag2-/- rats are suitable visualization models, which recapitulate wild type or immunodeficient populations respectively, for testing human smallpox vaccine and antiviral drugs.
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Changfa
authors.initials: C
authors.lastname: Fan
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Shuya
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Biocytogen Co., Ltd, Beijing, 101111, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zuo
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Susu
authors.initials: S
authors.lastname: Liu
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Zexu
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Fan
authors.affiliation: Biocytogen Co., Ltd, Beijing, 101111, China.
authors.forename: Chaoshe
authors.initials: C
authors.lastname: Guo
authors.affiliation: Biocytogen Co., Ltd, Beijing, 101111, China.
authors.forename: Yuelei
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Weijin
authors.initials: W
authors.lastname: Huang
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Baowen
authors.initials: B
authors.lastname: Li
authors.affiliation: Division of Animal Model Research, Institute for Laboratory Animal Resources, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Zhengming
authors.initials: Z
authors.lastname: He
authors.affiliation: Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Key Laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products, National Institutes for Food and Drug Control, Beijing, 100050, China.
authors.forename: Youchun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D057134:Antibodies, Neutralizing / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001483:Base Sequence; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D017930:Genes, Reporter; D005838:Genotype; D006801:Humans; D016867:Immunocompromised Host; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D061848:Optical Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D012899:Smallpox / Q000473:pathology* / Q000517:prevention & control / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014616:Vaccinia virus / Q000235:genetics / Q000472:pathogenicity*; D014709:Vero Cells
chemical_list: D057134:Antibodies, Neutralizing; D004268:DNA-Binding Proteins; C064655:V(D)J recombination activating protein 2