Submitted to: Virology Journal
Publication Type: Peer reviewed journal
Publication Acceptance Date: 7/31/2012
Publication Date: 8/6/2012
Citation: Neill, J.D., Newcomer, B.W., Marley, S.D., Ridpath, J.F., Givens, M.D. 2012. Greater numbers of nucleotide substitutions are introduced into the genomic RNA of bovine viral diarrhea virus during acute infections of pregnant cattle than of non-pregnant cattle. Virology Journal. 9:150 doi: 10.1186/1743-422x-9-150. Interpretive Summary: Bovine viral diarrhea virus (BVDV) is a ubiquitous viral pathogen of cattle worldwide. It spread readily between animals and between herds. Additionally, BVDV can infect pregnant cattle that can result in the birth of a calf that is persistently infected and spreads the virus for life. There is a great amount of sequence difference between strains of BVDV found in livestock herds and it is not known what really drives changes to occur. This study looked deeper into when the changes occurred and compared this to the number of changes that occur in single infections of non-pregnant cattle. This showed that the majority of changes occurred in the infection of the pregnant cow and not during the infection of the fetus. Also, the numbers of these changes were in the range of 2.5- to 8-fold higher than in a single infection of non-pregnant animals. These results show the importance of persistent infections in driving genetic change and the importance of screening herds for persistent infections and eliminating them.
Technical Abstract: Bovine viral diarrhea virus (BVDV) strains circulating in domestic livestock herds show significant sequence variation. Conventional wisdom states that most sequence variation arises during acute infections in response to immune or other environmental pressures. A recent study showed that more nucleotide changes were introduced into the BVDV genomic RNA during the establishment of a single fetal persistent infection than following a series of acute infections of naïve cattle. However, it was not known when nucleotide changes were introduced in pregnant cattle, whether changes occurred when the virus crossed the placenta and infected the fetus or during the acute infection of the dam. The sequence of the open reading frame (ORF) from viruses isolated from four acutely infected pregnant heifers following exposure to persistently infected (PI) calves was compared to the sequences of the virus from the progenitor PI calf and the virus from the resulting progeny PI calf to determine when genetic change was introduced. Additionally, the degree of genetic change was determined for viruses isolated from a pregnant PI cow and its PI calf, and three viruses isolated from acutely infected, non-pregnant cattle exposed to PI calves. Most genetic changes previously identified between the progenitor and progeny PI viruses were found to be in place in the acute phase viruses isolated from the dams six days post-exposure to the progenitor PI calf. Additionally, each progeny PI virus had two to three unique nucleotide substitutions that were introduced in crossing the placenta and infection of the fetus. The nucleotide sequence of two acute phase viruses isolated from steers exposed to PI calves revealed that six and seven nucleotide changes were introduced during the acute infection. The sequence of the BVDV-2 virus isolated from an acute infection of a PI calf (BVDV-1a) co-housed with a BVDV-2 PI calf had ten nucleotides that were different from the progenitor PI virus. Finally, the sequence of the virus isolated from a type 1b PI cow was compared to the sequence of the virus isolated from its PI calf at birth. Twenty nucleotide changes were identified in the PI virus of the calf. Taken together, these results demonstrate that nucleotide changes are introduced into the BVDV strains infecting pregnant cattle at rates of 2.3- to 8-fold higher than during the acute infection of non-pregnant animals.