Pathogenesis of Human and Bovine Cryptosporidium parvum in Gnotobiotic Pigs

To compare the pathogenesis of human genotype 1 (HuGl) and bovine genotype 2 (BoG2) Cryptosporidium parvum, neonatal gnotobiotic pigs were given 1-10 HuGl or BoG2 oocysts. The prepatent and patent periods were significantly longer for HuGl than for BoG2 C. parvum (prepatent, 8.6 vs. 5.6 days; patent, 16.6 vs. 10.3 days). BoG2-infected pigs developed signif- icantly more severe disease than did HuGl-infected pigs. BoG2 parasites were seen micro- scopically throughout the intestines during the prepatent and patent periods. HuGl parasites were only detected during the patent period in the ileum and colon but colonized the mucosal surface in significantly larger numbers than did BoG2. Moderate-to-severe villus/mucosal attenuation with lymphoid hyperplasia was seen throughout the intestines of BoG2-infected pigs, whereas lesions in HuGl-infected pigs were mild to moderate and restricted to the ileum and colon. These findings provide additional support for the hypothesis that human and bovine C. parvum genotypes may be separate species.

INFLUENCE OF TYPE 2 BOVINE VIRAL DIARRHEA VIRUS NPRO ON ENHANCEMENT OF BOVINE RESPIRATORY SYNCYTIAL VIRUS REPLICATION MEDIATED BY ANTAGONISM OF HOST CELL INTERFERON TYPE I RESPONSES

Bovine viral diarrhea virus (BVDV) is a member of the genus Pestivirus, Family Flaviviridae. The virus can infect many species of animals of the order Artiodactyla. The BVDV genome encodes an auto protease, Npro, that degrades interferon regulatory factor-3 (IRF-3) reducing type I interferon (IFN-I) production from host cells. Bovine respiratory syncytial virus (BRSV) is a member of the genus Pneumovirus, Family Paramyxoviridae. Concurrent infection with BVDV and BRSV causes more severe respiratory and enteric disease than infection with either virus alone. Our hypothesis was that Npro modulates the innate immune responses to BVDV infection and enhances replication of BVDV or BRSV co-infection. The noncytopathic BVDV2 viruses NY93/c N- Npro 18 EGFP (a mutant with modified Npro fused with enhanced green fluorescent protein), NY93 infectious clone (NY93/c), wild-type NY93-BVDV2 (NY93-wt), and BRSV were evaluated in this study. The objectives of this study were: (1) to characterize the replication kinetics and IFN-I induction in Madin-Darby bovine kidney (MDBK) cells following infection with each of the BVDV isolates, and (2) to characterize the influence of BVDV-mediated IFN-I antagonism on enhancement of BRSV replication in bovine turbinate (BT) cells. NY93/c N- Npro 18 EGFP replicated 0.4 – 1.6 TCID50 logs lower than NY93-wt in MDBK cells. NY93/c N- Npro 18 EGFP-infected MDBK cells synthesized IFN-I significantly higher than NY93/c- and NY93-wt-infected MDBK cells. BT cells co-infected with NY93/c N- Npro 18 EGFP/BRSV or NY93-wt/BRSV were evaluated to determine the effects of co-infection on BRSV replication and IFN-I induction in BT cells. BRSV RNA levels in NY93-wt/BRSV co-infected BT cells were 2.49, 2.79, and 2.89 copy number logs significantly greater than in NY93/c N- Npro 18 EGFP/BRSV co-infected BT cells on days 5, 7, and 9 post-infection, respectively. BVDV RNA levels in NY93/c N- Npro 18 EGFP-infected BT cells were 1.64 – 4.38 copy number logs lower than in NY93-wt-infected BT cells. NY93/c N- Npro 18 EGFP single and co-infected BT cells synthesized IFN-I significantly higher than NY93-wt single and co-infected BT cells. In summary, these findings suggest: (1) NY93/c N- Npro 18 EGFP BVDV2 induced higher levels of IFN-I than BVDV2-wt and may be useful as a safer, replicating BVDV vaccine, and (2) Enhancement of BRSV infection by BVDV co-infection is mediated by antagonism of IFN-I.

SCWDS BRIEFS: Volume 20, Number 2 (July 2004)

National Veterinary Services Laboratories in Ames, Iowa, confirmed vesicular stomatitis (VS) in horses at one premises in Texas. As of July 21, 2004, infected animals were identified on a total of 45 premises in Colorado (11), New Mexico (21), and Texas (13). These are the first reports of VS in livestock in the United States since the 1998 epizootic. SCWDS VS Studies Chronic Wasting Disease Developments: nearly 118,000 wild white-tailed deer, mule deer, and elk were tested in the United States from October 2002 to September 2003, with 592 animals testing positive for the CWD prion. More than $38,000,000 was spent by federal and state wildlife and animal health agencies on CWD-related activities during this same period. The Second International Chronic Wasting Disease Symposium, hosted by the Wisconsin Department of Natural Resources, will be held in Madison, Wisconsin, July 12-14, 2005. Crow Decoys Used in West Nile Virus Study Although Lyme disease caused by a spirochete bacterium, Borrelia burgdorferi, is relatively rare in the southeastern United States, a Lyme disease-like infection referred to as Southern Tick-Associated Rash Illness (STARI) and thought to be caused by Borrelia lonestari, has been recognized in people in this region. The Ohio Division of Wildlife joined SCWDS as an associate member beginning July 1, 2004. The Final Report of the 2003 Hemorrhagic Disease (HD) Surveillance project has been completed and distributed to all cooperators. New of Caroline Duffie, Robbie Edalgo and wife Jen, Clay George, Darrell Kavanaugh, Lynn Lewis-Weiss’s husband, Dr. Kevin Weiss, and Nate Mechlin. New SCWDS staff include Brian Chandler, Jay Cumbee, Ginger Goekjian, Bill Hamrick, Sabrina McGraw, Kerri Pedersen, and Ben Wilcox. Recent SCWDS Publications Available