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United States Department of Agriculture

Agricultural Research Service

Research Project: CONTROL OF GAMMAHERPESVIRUS-ASSOCIATED MALIGNANT CATARRHAL FEVER IN RUMINANTS

Location: Animal Diseases Research

Title: Ovine herpesvirus 2 replicates initially in the lung of experimentally infected sheep

Authors
item Li, Hong
item Cunha, Cristina
item Davies, C - WSU
item Gailbreath, Katherine
item Knowles, Donald
item Oaks, J - WSU
item Taus, Naomi

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 14, 2008
Publication Date: July 1, 2008
Citation: Li, H., Cunha, C.W., Davies, C.J., Gailbreath, K.L., Knowles Jr, D.P., Oaks, J.L., Taus, N.S. 2008. Ovine herpesvirus 2 replicates initially in the lung of experimentally infected sheep. Journal of General Virology. 89(7):1699-1708.

Interpretive Summary: Ovine herpesvirus 2 (OvHV-2) is a herpesvirus carried by sheep causing sheep-associated malignant catarrhal fever (SA-MCF), a frequently fatal disease in ruminants, such as cattle, bison and deer. Inability to grow the virus in culture has made it difficult to study viral replication. A recently developed system using aerosol inoculation of sheep with OvHV-2 in nasal secretions collected from naturally infected sheep during shedding events allowed us to determine the tissue site(s) where OvHV-2 initial replication takes place. In the study, we showed that OvHV-2 delivered through the nasal route by aeroslization resulted in infection in all lambs, but no infection was established by intravenous or intraperitoneal injection. In aerosolized lambs, while it was not detected initially in any other tissues, the viral DNA became detectable in the lung at 3 days after infection and reached peak levels at 7 days, and then declined at 9 days. A viral component (transcripts of a viral gene for a structural protein) representing replication was also detected only in lung tissues, and was positively correlated with viral DNA levels in the lungs. In addition, selected immune response genes were also highly expressed in the lung at 5 and 7 days after infection. The data indicate that lung is the primary replication site for OvHV 2 during initial infection in sheep and suggest that viral replication is promptly controlled by a host defense mechanism.

Technical Abstract: Ovine herpesvirus 2 (OvHV-2), a rhadinovirus in the gammaherpesvirus subfamily, is the causative agent of sheep-associated malignant catarrhal fever (SA-MCF), a frequently fatal lymphoproliferative disease primarily of ruminants worldwide. Inability to propagate the virus in vitro has made it difficult to study OvHV-2 replication. Aerosol inoculation of sheep with OvHV-2 from nasal secretions collected from naturally infected sheep during shedding episodes results in infection of naive sheep, providing an excellent system to study OvHV-2 initial replication in the natural host. In this study, we showed that OvHV-2 delivered through the nasal route by nebulization resulted in infection in all lambs, but no infection was established in any lambs after intravenous or intraperitoneal injection. In nebulized lambs, while it was not detected initially in any other tissues, OvHV-2 DNA became detectable in the lung at 3 days post infection (DPI), increased to about 900 copies at 5 DPI, reached peak levels (~7,500 copies) at 7 DPI, and then declined to an average of 800 copies at 9 DPI. Transcripts of OvHV-2 open reading frame 25 (coding for capsid protein), an indicator of virus replication, were only detected in lung tissues, and were positively correlated with OvHV-2 DNA levels in the lungs. In addition, selected immune response genes were also highly expressed in the lung at 5 and 7 DPI. The data indicate that lung is the primary replication site for OvHV 2 during initial infection in sheep and suggest that viral replication is promptly controlled by a host defense mechanism.

Last Modified: 8/29/2014
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