Reproductive consequences of infection with bovine viral diarrhea virus (Proceedings)
Bovine viral diarrhea virus (BVDV) has emerged as one of the most important infectious disease agents in cattle. The insidious nature of BVDV has led to substantial economic losses in both the dairy and beef industry on a worldwide level. Contrary to its name, BVDV has been associated with pathology in several physiological systems including the respiratory, hematological, immunological, neurological and reproductive systems. Reproductive losses may be the most economically important consequence associated with BVDV infection and evidence suggests the incidence of BVDV related reproductive losses are increasing in the United States (Evermann & Ridpath, 2002). In addition to reduced reproductive efficiency, BVDV uses the reproductive system to maintain and spread itself in the cattle population by inducing immunotolerance following fetal infection, resulting in birth of calves persistently infected with the virus. Cattle persistently infected with BVDV are the major source of virus spread within and between farms.
Reproductive losses associated with BVDV infection was described by Olafson et al (1946) in the first clinical description of BVDV. In this report, pregnant cows subclinically infected with BVDV often aborted 10 to 90 days later. Since that time, it has become evident that BVDV can cause a wide array of reproductive losses that are largely dependent on the time of gestation which infection occurs and the virus strain.
Infection Prior to Conception Through the Embryonic Stage (-9 to 45 days of gestation)Field and epidemiological studies suggest that BVDV can have a significant impact on early reproductive performance. In a group of seronegative cattle accidentally exposed to a persistently infected cow, conception rates in groups that seroconverted to BVDV before, during or after breeding were 78.6, 44.4 and 22.2% (Virakul et al., 1988). Those seroconverting to BVDV at breeding or soon after breeding were less likely to conceive than those who had seroconverted prior to breeding. Similarly, McGowan et al. (1993) compared BVDV seropositive heifers to heifers that seroconverted between breeding and pregnancy diagnosis at 51 days post insemination and found the pregnancy rate was significantly reduced in the seroconverting heifers. However, no difference was found with cows under the same circumstances. Houe et al (1993) identified and defined a specific risk period for BVDV infection in dairy herds in which cattle persistently infected with BVDV were found. The risk period was defined during the 2-year study period as the period of time previous to when the oldest PI animal was 6 months old. In all herds studied, conception rates were significantly lower during the defined risk period than the post-risk period. In an experimental study looking at BVDV infection around breeding, conception rates in heifers infected intranasally nine days before insemination was 44% compared to 79% for the control group (McGowan et al., 1993). The reduction in conception rates was attributed to either failure of fertilization or early embryonic death. In the same report, the conception rate in heifers exposed to a persistently infected cow and calf four days following insemination was 60%. However, significant embryo loss was experienced in this group resulting in a day 77-pregnancy rate of only 33% compared to 79% for the control group.
The mechanism for decreased conception rates is not clear but may depend on the time of infection with respect to the stage of early reproductive events. Virus has been localized in ovarian tissue for prolonged periods of time following acute infection with cytopathic BVDV (Grooms et al., 1998a) and noncytopathic virus (Grooms et al., 1998b). Exposure of developing oocytes to BVDV could result in reduced survivability either through direct cell damage or indirectly through changes in the local environment of the oocyte. Following acute infection with BVDV, interstitial oophoritis has been described with lesions lasting up to 60 days (Grooms et al., 1998a). Significant long-term oophoritis could result in ovarian malfunction with subsequent poor conception rates. Limited information is available on ovarian function following BVDV infection. In a study of cattle being superovulated while undergoing experimental challenge with BVDV, the number of palpable corpora lutea and recovered embryos was significantly reduced when compared to noninfected cows also undergoing superovulation (Kafi et al., 1994). Infection and subsequent viremia during the preovulatory phase can reduce the rate of follicle growth (Grooms et al., 1998c, Fray et al., 1999). Modulation of ovarian hormone secretion has been demonstrated following acute BVDV infection and has been postulated as a potential cause of BVDV induced infertility (Fray et al., 1999, Fray et al., 2000, Fray et al., 2002). Taken together, these studies suggest that ovarian dynamics may be changed in cattle infected with BVDV, and these changes may subsequently lead to transient or long-term decreases in fertility.
Several in vitro studies have been undertaken to elucidate the effects of BVDV on early reproductive function. Ova exposed to BVDV in vitro can have virus particles attached to the zona pellucida (Gillespie et al., 1990). However, in vitro studies have shown that the intact zona pellucida protects the developing embryonic cells from BVDV infection, allowing normal development to continue (Singh et al., 1982, Potter et al., 1984). In morula and blastocyst stage bovine embryos with the zona pellucida intact or damaged, no cytopathic effects were seen for 48 hours following exposure to cytopathic BVDV (Bilenski et al., 1988). Similarly, zona pellucida intact embryos exposed to noncytopathic BVDV infected bovine oviductal epithelial cells for 7 days showed no adverse effects in their rates of development (Zurovac et al., 1994). In contrast, blastocysts hatched from the zona pellucida (day 8 of gestation) have been shown to decrease viability when exposed to cytopathic BVDV in vitro. In the same study, noncytopathic BVDV did not decrease blastocyst survivability (Brock & Stringfellow, 1993). These studies suggest that the zona pellucida protects the developing embryo from direct effects of BVDV. However, following removal of the zona pellucida, cytopathic BVDV may have detrimental effects on survivability of blastocysts. Noncytopathic BVDV has not been shown to have the same effects. As noncytopathic BVDV is the most common virus isolated in acute outbreaks of BVDV, and has been the biotype associated with reported decreases in conception rates, further characterization of the effect of noncytopathic BVDV on the early stages of the developing embryo is necessary.