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Characterization of Monkeypox virus infection in African rope squirrels (Funisciurus sp.).

Abstract Monkeypox (MPX) is a zoonotic disease endemic in Central and West Africa and is caused by Monkeypox virus (MPXV), the most virulent Orthopoxvirus affecting humans since the eradication of Variola virus (VARV). Many aspects of the MPXV transmission cycle, including the natural host of the virus, remain unknown. African rope squirrels (Funisciurus spp.) are considered potential reservoirs of MPXV, as serosurveillance data in Central Africa has confirmed the circulation of the virus in these rodent species [1,2]. In order to understand the tissue tropism and clinical signs associated with infection with MPXV in these species, wild-caught rope squirrels were experimentally infected via intranasal and intradermal exposure with a recombinant MPXV strain from Central Africa engineered to express the luciferase gene. After infection, we monitored viral replication and shedding via in vivo bioluminescent imaging, viral culture and real time PCR. MPXV infection in African rope squirrels caused mortality and moderate to severe morbidity, with clinical signs including pox lesions in the skin, eyes, mouth and nose, dyspnea, and profuse nasal discharge. Both intranasal and intradermal exposures induced high levels of viremia, fast systemic spread, and long periods of viral shedding. Shedding and luminescence peaked at day 6 post infection and was still detectable after 15 days. Interestingly, one sentinel animal, housed in the same room but in a separate cage, also developed severe MPX disease and was euthanized. This study indicates that MPXV causes significant pathology in African rope squirrels and infected rope squirrels shed large quantities of virus, supporting their role as a potential source of MPXV transmission to humans and other animals in endemic MPX regions.
PMID
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Authors

Mayor MeshTerms
Keywords
Journal Title plos neglected tropical diseases
Publication Year Start




PMID- 28827792
OWN - NLM
STAT- MEDLINE
DA  - 20170822
DCOM- 20170907
LR  - 20170917
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Linking)
VI  - 11
IP  - 8
DP  - 2017 Aug
TI  - Characterization of Monkeypox virus infection in African rope squirrels
      (Funisciurus sp.).
PG  - e0005809
LID - 10.1371/journal.pntd.0005809 [doi]
AB  - Monkeypox (MPX) is a zoonotic disease endemic in Central and West Africa and is
      caused by Monkeypox virus (MPXV), the most virulent Orthopoxvirus affecting
      humans since the eradication of Variola virus (VARV). Many aspects of the MPXV
      transmission cycle, including the natural host of the virus, remain unknown.
      African rope squirrels (Funisciurus spp.) are considered potential reservoirs of 
      MPXV, as serosurveillance data in Central Africa has confirmed the circulation of
      the virus in these rodent species [1,2]. In order to understand the tissue
      tropism and clinical signs associated with infection with MPXV in these species, 
      wild-caught rope squirrels were experimentally infected via intranasal and
      intradermal exposure with a recombinant MPXV strain from Central Africa
      engineered to express the luciferase gene. After infection, we monitored viral
      replication and shedding via in vivo bioluminescent imaging, viral culture and
      real time PCR. MPXV infection in African rope squirrels caused mortality and
      moderate to severe morbidity, with clinical signs including pox lesions in the
      skin, eyes, mouth and nose, dyspnea, and profuse nasal discharge. Both intranasal
      and intradermal exposures induced high levels of viremia, fast systemic spread,
      and long periods of viral shedding. Shedding and luminescence peaked at day 6
      post infection and was still detectable after 15 days. Interestingly, one
      sentinel animal, housed in the same room but in a separate cage, also developed
      severe MPX disease and was euthanized. This study indicates that MPXV causes
      significant pathology in African rope squirrels and infected rope squirrels shed 
      large quantities of virus, supporting their role as a potential source of MPXV
      transmission to humans and other animals in endemic MPX regions.
FAU - Falendysz, Elizabeth A
AU  - Falendysz EA
AUID- ORCID: http://orcid.org/0000-0003-2895-8918
AD  - US Geological Survey, National Wildlife Health Center, Madison, Wisconsin, United
      States of America.
FAU - Lopera, Juan G
AU  - Lopera JG
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, University
      of Wisconsin, Madison, Wisconsin, United States of America.
FAU - Doty, Jeffrey B
AU  - Doty JB
AD  - Centers for Disease Control and Prevention, Atlanta, Georgia, United States of
      America.
FAU - Nakazawa, Yoshinori
AU  - Nakazawa Y
AD  - Centers for Disease Control and Prevention, Atlanta, Georgia, United States of
      America.
FAU - Crill, Colleen
AU  - Crill C
AD  - US Geological Survey, National Wildlife Health Center, Madison, Wisconsin, United
      States of America.
FAU - Lorenzsonn, Faye
AU  - Lorenzsonn F
AD  - US Geological Survey, National Wildlife Health Center, Madison, Wisconsin, United
      States of America.
FAU - Kalemba, Lem's N
AU  - Kalemba LN
AD  - University of Kinshasa, Kinshasa, Democratic Republic of Congo.
FAU - Ronderos, Monica D
AU  - Ronderos MD
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, University
      of Wisconsin, Madison, Wisconsin, United States of America.
FAU - Mejia, Andres
AU  - Mejia A
AD  - Animal Services (Pathology), Wisconsin National Primate Research Center,
      University of Wisconsin, Madison, Wisconsin, United States of America.
FAU - Malekani, Jean M
AU  - Malekani JM
AD  - University of Kinshasa, Kinshasa, Democratic Republic of Congo.
FAU - Karem, Kevin
AU  - Karem K
AD  - Centers for Disease Control and Prevention, Atlanta, Georgia, United States of
      America.
FAU - Carroll, Darin S
AU  - Carroll DS
AD  - Centers for Disease Control and Prevention, Atlanta, Georgia, United States of
      America.
FAU - Osorio, Jorge E
AU  - Osorio JE
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, University
      of Wisconsin, Madison, Wisconsin, United States of America.
FAU - Rocke, Tonie E
AU  - Rocke TE
AD  - US Geological Survey, National Wildlife Health Center, Madison, Wisconsin, United
      States of America.
LA  - eng
PT  - Journal Article
DEP - 20170821
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Antibodies, Viral)
RN  - 0 (DNA, Viral)
SB  - IM
MH  - Africa, Central
MH  - Africa, Western
MH  - Animals
MH  - Antibodies, Viral/blood
MH  - DNA, Viral/blood
MH  - Humans
MH  - Monkeypox/*veterinary
MH  - Monkeypox virus/*physiology
MH  - Sciuridae/immunology/*virology
MH  - Virus Replication
MH  - Virus Shedding
PMC - PMC5578676
EDAT- 2017/08/23 06:00
MHDA- 2017/09/08 06:00
CRDT- 2017/08/23 06:00
PHST- 2017/03/02 [received]
PHST- 2017/07/17 [accepted]
PHST- 2017/08/31 [revised]
AID - 10.1371/journal.pntd.0005809 [doi]
AID - PNTD-D-17-00305 [pii]
PST - epublish
SO  - PLoS Negl Trop Dis. 2017 Aug 21;11(8):e0005809. doi:
      10.1371/journal.pntd.0005809. eCollection 2017 Aug.