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2017 ; 8
(ä): 1721
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Gastrointestinal Tract As Entry Route for Hantavirus Infection
#MMPMID28943870
Witkowski PT
; Perley CC
; Brocato RL
; Hooper JW
; Jürgensen C
; Schulzke JD
; Krüger DH
; Bücker R
Front Microbiol
2017[]; 8
(ä): 1721
PMID28943870
show ga
Background: Hantaviruses are zoonotic agents that cause hemorrhagic fevers and
are thought to be transmitted to humans by exposure to aerosolized excreta of
infected rodents. Puumala virus (PUUV) is the predominant endemic hantavirus in
Europe. A large proportion of PUUV-infected patients suffer from gastrointestinal
symptoms of unclear origin. In this study we demonstrate that PUUV infection can
occur via the alimentary tract. Methods: We investigated susceptibility of the
human small intestinal epithelium for PUUV infection and analyzed the resistance
of virions to gastric juice. As model for intestinal virus translocation we
performed infection experiments with human intestinal Caco-2 monolayers. In
animal experiments we infected Syrian hamsters with PUUV via the intragastric
route and tested seroconversion and protective immunity against subsequent Andes
virus challenge. Results: PUUV retained infectivity in gastric juice at pH >3.
The virus invaded Caco-2 monolayers in association with endosomal antigen EEA1,
followed by virus replication and loss of epithelial barrier function with
basolateral virus occurrence. Cellular disturbance and depletion of the tight
junction protein ZO-1 appeared after prolonged infection, leading to paracellular
leakage (leak flux diarrhea). Moreover, animal experiments led to dose-dependent
seroconversion and protection against lethal Andes virus challenge. Conclusions:
We provide evidence that hantavirus can infect the organism via the alimentary
tract and suggest a novel aspect of hantavirus infection and pathogenesis.
Significance: Hantaviruses are zoonotic pathogens causing severe hemorrhagic
fevers worldwide. They are transmitted to humans by small mammals. To date, these
viruses were thought to infect exclusively through the airborne route by
inhalation of aerosols from infectious animal droppings or by rodent bites. In
our work we could show that the alimentary tract is an alternative path of
infection for hantaviruses, meaning a new association of virus and disease. These
findings have impact on current textbook knowledge and bring many implications
for hantavirus epidemiology and outbreak prevention measures.