1a. Objectives (from AD-416):
Objective 1: Determine the impact of variant and emerging viruses on the development and control of respiratory disease in ruminants. Develop means to detect and survey for variant viruses and develop models for evaluating infections with emerging variant viruses. Subobjectives: (1a) Determine impact of variant and emerging viruses; (1b) Improve current surveillance methods and diagnostic tools used to detect and control emerging viruses. Objective 2: Elucidate the host-pathogen interactions associated with the Bovine Respiratory Disease Complex (BRDC) by defining host pathways modulated as a result of viral infections and characterizing the role of stress and immunological related host effector molecules in BRDC. Subobjectives: (2a) Define interactions of viral pathogens that may contribute to the development of respiratory disease; (2b) Define modulation of host immune response to viral infection associated with stress caused by vitamin D insufficiency. Objective 3: Evaluate formulations and delivery systems for vaccination of neonates by identifying means to modulate stress and immunological factors associated with BRDC. Generate identification criteria and means to generate “vaccine ready” calves to develop intervention strategies for controlling viral respiratory infections of ruminants. Subobjectives: (3a) Identify factors, associated with common management practices, that modulate immune function in neonatal calves; (3b) Evaluate candidate vaccine for use in calves.
1b. Approach (from AD-416):
The goal of this project is to reduce the incidence and impact of viral infections in ruminants with particular emphasis on viral infections that contribute to respiratory disease in cattle. The project encompasses three distinct but interrelated research efforts. The first is to determine the incidence and impact of variant viruses, such as subgenotypes of bovine viral diarrhea virus (BVDV), and emerging viruses, such as HoBi-like viruses, to bovine respiratory disease. The purpose of this research is to determine if new antigens, representing variant and emerging viruses, need to be included in vaccines. The second is to examine the interaction of host and virus in respiratory disease. Included in this effort will be the study of host immune dysfunction, resulting from viral infection, nutrition, or stress. The purpose of this research is to define factors that contribute to respiratory disease in order to develop means of intervention that negate or ameliorate those factors. The third is to determine means by which host resistance to viral infection can be enhanced with emphasis on improving protective innate and acquired immune responses in calves. The information generated from these three research areas will be used in the development of intervention strategies to control and eliminate viral pathogens. Improved control of viral pathogens will benefit consumers by ensuring a healthful food supply, enhance animal health and well-being, and reduce production costs for farmers and ranchers.
3. Progress Report:
A study comparing antigenic characteristics of Bovine viral diarrhea virus 1 and 2 (BVDV-1, -2) strains and HoBi virus was completed and the manuscript accepted for publication. The comparison was based on detection of HoBi virus and antibodies against it by commercial enzyme-linked immunosorbent assays (ELISAs) and the level of cross-neutralizing antibodies present in sera from animals vaccinated with killed BVDV. The results of this study indicate that detection and control of HoBi virus infections in cattle requires the development of new diagnostic reagents and reformulation of current vaccines. A manuscript comparing BVDV and HoBi-like virus infection of calves has been accepted for publication. In vivo studies of the impact of HoBi like infections on the immune system, including the generation of immunotolerant persistently infected cattle, have been started. BVDV isolated from bison, mountain goat and big horn sheep have been acquired and preliminary sequencing has begun. Studies of single infection of cattle with BVDV and BRSV have been completed. The transcriptomes of circulating B, T and monocyte cells of cattle infected with either high or low virulence BVDV have been generated. Models to study in vitro dual infection of cells infected with both BVDV and BRSV are under development. Studies of BVDV infection in macrophages and BRSV infection in macrophages have been completed and a manuscript has been drafted. A new component of Objective 2 will be examining host genetic markers that are associated with increased susceptibility or resistance to BRDC. Research milestones specifically addressing these contributions will be written for FY13.
1. Mechanism of Bovine Viral Diarrhea (BVDV) suppression of response to a secondary bacterial infection. The immune system consists of two branches, the innate immune system and the acquired immune system. The innate immune system is the first line of defense against infection. One of the side effects of infection with BVDV is suppression of the immune system and it is theorized that this suppression reduces the ability of cattle to fight off bacterial infections. ARS researchers at Ames, Iowa identified specific functions of the innate immune system that are affected by BVDV infection. Identification of these functions will contribute to development of means to block viral pathology.
2. Diagnostics to detect HoBi like viruses. A newly emerging type of virus, distantly related to BVDV, has been isolated from cattle in South America, Southeast Asia and Europe. The clinical presentation following infection with this type of virus, known as HoBi-like viruses, is very similar to that seen following infection with BVDV. Like BVDV, HoBi-like viruses cause immune suppression and can establish life long persistent infection in cattle. HoBi like viruses have not yet been detected in the U.S. ARS researchers at Ames, Iowa have developed tests to provide diagnosticians and regulatory agencies with tools to screen imported animals and animal products to prevent introduction of HoBi like viruses into the U.S. and means to detect and quickly control introduction if it does occur.
Bauermann, F.V., Flores, E.F., Ridpath, J.F. 2012. Antigenic relationships between bovine viral diarrhea virus 1 and 2 and HoBi virus: Possible impacts on diagnosis and control. Journal of Veterinary Diagnostic Investigation. 24(2):253-261.