Fact Sheet No. 3: Bovine Virus Diarrhea: Mucosal Disease and Persistent Infection
By Bill Kvasnicka, DVM Extension Veterinarian University of Nevada - Reno

Description and Cause

It has been almost 20 years since persistent infection with noncytopathic BVDV was reported. This condition occurs when a fetus is infected with noncytopahic BVDV during the first four months of development. Usually, the fetal infection follows an acute infection of a susceptible heifer or cow. For most midwestern beef herds, this means the dam was infected with BVDV during the summer or early fall. Persistent infection lasts for life. Persistently infected cows give birth to persistently infected calves. Persistently infected bulls seldom sire persistently infected calves. Persistently infected cattle spread disease, and it is desirable to eliminate them from a herd. This can be done by testing for persistent infection or by vaccinating the herd for BVD at regular intervals. Using the latter approach takes longer, but it is effective and economical.

Recent progress on persistent infection has focused on epidemiologic aspects of the condition. Most investigators report that persistent infection is rare and that persistently infected cattle have a short life span. The basis for this is the infrequent identification of persistently infected cattle. Also, most persistently infected cattle that have been identified were less than one year of age. Under experimental and field conditions, few persistently infected cattle survive past three years of age. This information has practical value when a veterinarian suspects a persistently infected animal in a herd. When testing for persistent infection, concentrate on the calves. Then test the dams of positive calves. Viral isolation is the test used commonly for identification of persistent infection. Other methods for identification of persistent infection include ELISA, nucleic acid hybridization, and polymerase chain reaction amplification. In dairy herds, a milk sample from the bulk tank can be used to test for persistent infection in the herd.

Mucosal disease is still thought to occur only in persistently infected cattle that become superinfected with cytopathic BVDV. Most outbreaks of mucosal disease originate when noncytopathic BVDV in a persistently infected animal mutates to form cytopathic BVDV. This mutation occurs in a region of the viral RNA that codes for a protein that is not involved with viral neutralization. Thus, in most outbreaks of mucosal disease, the cytopathic and noncythpathic BVDV will be antigenically identical by viral neutralization. Mucosal disease occurs rarely after vaccination with modified-live virus vaccines. Postvaccinal mucosal disease usually occurs 2 to 4 weeks after vaccination or 3 to 6 months after vaccination. Antigenically distinct viral pairs are isolated from cattle that develop mucosal disease 2 to 4 weeks after vaccination. Antigenically identical viral pairs are isolated from cattle that develop mucosal disease 3 to 6 months after vaccination.

Information on BVDV-Type 2

Bovine viral diarrhea virus is now segregated into two genotypes, BVDV-type 1 and BVDV-type 2. Type 1 BVDV include vaccine and laboratory reference viruses BVDV-NADL, BVDV-Singer, BVDV-C24V, and BVDV-NY1. Type 2 BVDV are not used for laboratory diagnostic purposes or for vaccines. However, this is likely to change in the near future. The good news for now is that the viral genotypes share some antigenic determinants. Antibody raised against BVDV-type 1 will neutralize infectivity of BVDV-type 2; however, the efficiency of viral neutralization is less than with BVDV-type 1. This means that current diagnostic reagents can detect BVDV-type 2, and current vaccines will stimulate cross-reactive antibody that offer some protection from disease.

Most isolates of BVDV-type 2 are noncytopathic in cell culture, but cytopathic BVDV-type 2 exist. The clinical diseases associated with BVDV-type 2 are similar to those induced by BVDV-type 1. Some isolates of BVDV-type 2 have come from herds with subclinical to mild disease. Persistently infected cattle and mucosal disease occur with BVDV-type 2. Abortions and other signs of reproductive failure occur with BVDV-type 2. Some exceptionally virulent BVDV-type 2 have been isolated from calves and adult cattle that had severe disease. Signs associated with virulent BVDV-type 2 infections include diarrhea, thrombocytopenia, to those of mucosal disease, but only noncytopathic BVDV-type 2 was isolated from their tissues. Thus, BVDV-type 2 appear to be a group of viruses whose members vary considerably in virulence.

Virulent type 2 BVDV have caused substantial economic losses to individual producers and have spread among neighboring farms to cause substantial losses over geographic areas. At this time, there is a need to establish both the geographic distribution of BVDV-type 2 and the impact these BVDV have on beef and dairy production. Outbreaks of acute BVD that are unusually severe clinically, or are mild clinically but have an unusually high morbidity, are of interest. A recently developed viral neutralization test can be used to identify the viral type that caused a disease outbreak. This test uses convalescent serum. However, viral isolation is preferred for typing BVDV. Polymerase chain reaction amplification of selected segments of viral RNA is the procedure primarily used to type BVDV. This procedure is expensive, time-consuming, and requires substantial technical expertise. For these reasons, it is best to contact state or federal diagnostic laboratories before submitting BVDV for typing. Curiosity does not warrant the time and expense of viral typing. Unusually severe outbreaks of disease, and instances of vaccination failure, do warrant viral typing.

Information on Diagnostic Test and Vaccination

Diagnostic tests in routine use for detection of BVDV or antibody against BVDV are the same as those used for the last 10 years. A few diagnostic laboratories have the capability to perform polymerase chain reaction (PCR) amplification of nucleic acid. This procedure uses two nucleic acid primers (usually 18 to 30 bases) to specifically bind to the DNA or RNA of a target organism. After binding, the primers are separated from each other, often by several hundred bases of the target nucleic acid. An enzyme closes that separation by adding the appropriate bases until enough of the newly formed segments of nucleic acid accumulate for detection. The PCR test is sensitive and specific.

Vaccines

Vaccines for BVD have changed little in the last few years. Improvements in stabilization of inactivated vaccines, and in adjuvant system, have been made. These improvements have had a positive effect on immunogenicity. The growing appreciation for the antigenic and genomic diversity that exists among BVDV will stimulate production of new vaccines made by classical methods. Advances in biotechnology may soon lead to vaccines for BVD that employ recombinant organisms or products from those organisms. Vaccination for BVD remains controversial. There are advantages and disadvantages associated with both inactivated and modified-live virus vaccines. Clearly, there is no vaccine that is superior in all circumstances. Similarly, the ideal vaccination program for BVD does not exist. Thus, vaccine use for BVD remains dependent on the judgement of the veterinarian.