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Journal of Virology, November 1999, p. 9576-9583, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Pathogenesis of Experimental Rhesus
Cytomegalovirus Infection
Kristen M.
Lockridge,
Getachew
Sequar,
Shan Shan
Zhou,
Yujuan
Yue,
Carol P.
Mandell, and
Peter A.
Barry*
Center for Comparative Medicine, Department
of Medical Pathology, University of California
Davis, Davis,
California
Received 25 May 1999/Accepted 28 July 1999
Human cytomegalovirus (HCMV) establishes and maintains a lifelong
persistence following infection in an immunocompetent host. The
determinants of a stable virus-host relationship are poorly defined. A
nonhuman primate model for HCMV was used to investigate virological and
host parameters of infection in a healthy host. Juvenile rhesus
macaques (Macaca mulatta) were inoculated with rhesus
cytomegalovirus (RhCMV), either orally or intravenously (i.v.), and
longitudinally necropsied. None of the animals displayed clinical signs
of disease, although hematologic abnormalities were observed
intermittently in i.v. inoculated animals. RhCMV DNA was detected
transiently in the plasma of all animals at 1 to 2 weeks postinfection
(wpi) and in multiple tissues beginning at 2 to 4 wpi. Splenic tissue
was the only organ positive for RhCMV DNA in all animals. The location
of splenic cells expressing RhCMV immediate-early protein 1 (IE1) in
i.v. inoculated animals changed following inoculation. At 4 to 5 wpi,
most IE1-positive cells were perifollicular, and at 25 wpi, the
majority were located within the red pulp. All animals developed
anti-RhCMV immunoglobulin M (IgM) antibodies within 1 to 2 wpi and IgG
antibodies within 2 to 4 wpi against a limited number of viral
proteins. Host reactivity to RhCMV proteins increased in titer (total
and neutralizing) and avidity with time. These results demonstrate that
while antiviral immune responses were able to protect from disease,
they were insufficient to eliminate reservoirs of persistent viral gene expression.
*
Corresponding author. Mailing address: Center for
Comparative Medicine, University of California, Davis, CA 95616. Phone: (530) 752-6912. Fax: (530) 752-7914. E-mail:
pabarry{at}ucdavis.edu.
Journal of Virology, November 1999, p. 9576-9583, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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