Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 24, 2014
Publication Date: April 1, 2014
Citation: Deaton, M.K., Spear, A., Faaberg, K.S., Pegan, S.D. 2014. The vOTU domain of highly-pathogenic porcine reproductive and respiratory syndrome virus displays a differential substrate preference. Virology. 454-455:247-253. Interpretive Summary: Porcine reproductive and respiratory syndrome is a major problem for the pork industry. The disease is caused by a virus called porcine reproductive and respiratory syndrome virus (PRRSV). In the past 5-7 years, a new version of this virus has caused deadly outbreaks in China and other parts of Asia. It is unknown why this new strain of virus can cause such lethal disease. In this report, we determined that an enzyme from porcine reproductive and respiratory syndrome virus can interrupt some of the normal alarm systems that detect virus infection. Without the signals, the immune system has a harder time fighting the infection. We also found that the new strain of virus that causes virulent disease can block these alarm signals even better than the original virus. This might explain why this new strain virus can cause deadly disease, and why the older types of this virus are not so lethal.
Technical Abstract: Arterivirus genus member Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically devastating disease that presents global concerns to the pork industry, which have been exacerbated by the emergence of a highly pathogenic PRRSV strain (HP-PRRSV) in China and Southeast Asia. Within the large multifunctional nonstructural protein 2 of this positive-sense, single stranded virus, a deubiquitinating enzyme domain has been identified and classified as a member of the viral ovarian tumor (vOTU) protease superfamily. vOTU domains have been implicated as a potential virulence factor and identified in members of various viral families. Recently, vOTU domains originating from nairoviruses and a tymovirus were found to greatly vary in their preference for their host ubiquitin (Ub) and Ub-like substrates. Since various strains of PRRSV have large well-demonstrated variations in virulence, the specificity of vOTU domains from the highly pathogenic JXwn06 strain and the North American VR-2332 strain were determined. While both vOTU domains showed de-ubiquitinating activity, HP-PRRSV differed in its preference for certain polyubiquitin linkages tied to innate immune response regulation. This represents the first report of a biochemical activity unique to HP-PRRSV that has direct implications for a potential increase in immunosuppression and virulence exhibited by these Asian strains.