Porcine Parvovirus - Pathogenesis

Pathogenesis

Dams are susceptible to PPV-induced reproductive failure if infected anytime during about the first half of gestation. This interval of maternal susceptibility is indicated by the collective results of several experimental studies, by in-depth epidemiological investigations, and by estimates of the time of death of fetuses collected during epidemiological surveys. Consequences of maternal infection during this interval are embryonic and fetal death followed by resorption and mummification respectively. Transplacental infection also follows maternal exposure after midgestation, but fetuses usually survive without obvious clinical effects in utero. The likely reason is that transplacental infection often requires 10–14 days or longer, and by 70 days of gestation most fetuses are able to develop a protective immunologic response to the virus. In general, fetuses experimentally infected by transuterine inoculation of the virus have died when infected before day 70 of gestation, but they have survived and produced antibody when infected later in gestation. A strain of PPV of slightly greater virulence also has been reported. The usual consequences of infection at different stages of gestation are summarized in Table 1.

When only part of a litter is infected transplacentally, as is often the case, one or more littermates are frequently infected by subsequent intrauterine spread of virus. The same would apply if initial infection were through contaminated semen. As a result, any combination or all of the sequelae indicated in Table 1 can develop in the same litter. Intrauterine dissemination is probably less common when early embryos are infected because they are quickly resorbed after death, effectively removing the intrauterine reservoir of virus. In such cases there is no evidence at farrowing for the cause of fewer pigs per litter.

aIntervals are approximations.

bAssuming transplacental infections 10–14 days after maternal exposure.

The effect, if any, of PPV on the ovum before ovulation is unknown. The virus adheres tenaciously to the external surface of the zona pellucida of the fertilized porcine ovum, and although it apparently cannot penetrate this layer, speculation is that it could pose a threat to the embryo after hatching.

Despite strong circumstantial evidence, a direct causal role of PPV-contaminated semen in reproductive failure has not been established unequivocally. The zona pellucida could protect the early embryo while local immunity is developing. Conversely, the virus may cause uterine changes incompatible with gestation. In any event, a female infected through semen provides a focus of infection for others.

With the possible exception of the uterine changes alluded to in the preceding paragraph, PPV-induced reproductive failure is caused by the direct effect of the virus on the conceptus. In the absence of an immune response, the virus replicates extensively throughout these tissues. By the time the conceptus dies, most of its cells contain large quantities of intracytoplasmic viral antigen that can be demonstrated by IF microscopy. The relative lack of nuclear fluorescence at the time of death, compared to earlier stages of the disease, indicates that when the conceptus is severely affected, mitotic activity and the associated conditions necessary for viral replication are suppressed more than phagocytic activity.

Death of the conceptus probably results from the collective damage by the virus to a variety of tissues and organs, including the placenta. However, in the absence of an immune response, changes in almost any vital organ are probably sufficient to eventually cause death. One of the most striking features of viral distribution is the extensive involvement of endothelium. This seems to preclude further development of the vascular network of the conceptus. Preparation for cellular mitosis (i.e., the S phase) results in concomitant viral replication and cell death. Damage to the fetal circulatory system is indicated by edema, hemorrhage, and the accumulation of large amounts of serosanguineous fluids in body cavities. Necrosis of the endothelium is microscopically evident.

The mechanism of transplacental infection has been investigated by using IF microscopy to identify infected cells in maternal and fetal tissues at progressively longer intervals after maternal oronasal exposure. Examination of tissues contiguous with the maternal-fetal junction revealed viral antigen in endothelial and mesenchymal cells of the chorion, with increasing involvement of these tissues at progressively later stages of gestation. Viral antigen was never detected unequivocally in either uterine epithelium or trophectoderm. Consequently, there was no evidence for maternalfetal transfer of the virus by replicating through these tissues. However, this route cannot be excluded, since only a small part of the total area of contact was examined. Transfer of the virus within macrophages has been considered. Whatever the route, maternal viremia seems a likely prerequisite for transplacental infection.