Humanized Mice Reproduce Acute and Persistent Human Adenovirus Infection
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Humanized Mice Reproduce Acute and Persistent Human Adenovirus Infection. / Rodríguez, Estefanía; Ip, Wing Hang; Kolbe, Viktoria; Hartmann, Kristin; Pilnitz-Stolze, Gundula; Tekin, Nilgün; Gómez-Medina, Sergio; Muñoz-Fontela, César; Krasemann, Susanne; Dobner, Thomas.
In: J INFECT DIS, Vol. 215, No. 1, 01.01.2017, p. 70-79.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Humanized Mice Reproduce Acute and Persistent Human Adenovirus Infection
AU - Rodríguez, Estefanía
AU - Ip, Wing Hang
AU - Kolbe, Viktoria
AU - Hartmann, Kristin
AU - Pilnitz-Stolze, Gundula
AU - Tekin, Nilgün
AU - Gómez-Medina, Sergio
AU - Muñoz-Fontela, César
AU - Krasemann, Susanne
AU - Dobner, Thomas
N1 - © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Severe human adenovirus (HAdV) infections are an increasing threat for immunosuppressed individuals, particularly those who have received stem cell transplants. It has been previously hypothesized that severe infections might be due to reactivation of a persistent infection, but this hypothesis has been difficult to test owing to the lack of a permissive in vivo model of HAdV infection. Here we established a humanized mouse model that reproduces features of acute and persistent HAdV infection. In this model, acute infection correlated with high mortality, weight loss, liver pathology, and expression of viral proteins in several organs. In contrast, persistent infection was asymptomatic and led to establishment of HAdV-specific adaptive immunity and expression of early viral genes exclusively in the bone marrow. These findings validate the use of humanized mice to study acute and persistent HAdV infection and strongly suggest the presence of cellular reservoirs in the bone marrow.
AB - Severe human adenovirus (HAdV) infections are an increasing threat for immunosuppressed individuals, particularly those who have received stem cell transplants. It has been previously hypothesized that severe infections might be due to reactivation of a persistent infection, but this hypothesis has been difficult to test owing to the lack of a permissive in vivo model of HAdV infection. Here we established a humanized mouse model that reproduces features of acute and persistent HAdV infection. In this model, acute infection correlated with high mortality, weight loss, liver pathology, and expression of viral proteins in several organs. In contrast, persistent infection was asymptomatic and led to establishment of HAdV-specific adaptive immunity and expression of early viral genes exclusively in the bone marrow. These findings validate the use of humanized mice to study acute and persistent HAdV infection and strongly suggest the presence of cellular reservoirs in the bone marrow.
KW - Acute Disease
KW - Adaptive Immunity
KW - Adenovirus Infections, Human
KW - Adenoviruses, Human
KW - Animals
KW - Asymptomatic Infections
KW - Bone Marrow
KW - DNA, Viral
KW - Disease Models, Animal
KW - Humans
KW - Immunocompromised Host
KW - Liver
KW - Mice
KW - Mice, Transgenic
KW - Viral Load
KW - Viremia
KW - Journal Article
U2 - 10.1093/infdis/jiw499
DO - 10.1093/infdis/jiw499
M3 - SCORING: Journal article
C2 - 28077585
VL - 215
SP - 70
EP - 79
JO - J INFECT DIS
JF - J INFECT DIS
SN - 0022-1899
IS - 1
ER -