The pathogenesis of porcine reproductive and respiratory syndrome (PRRS) is fully determined by the intriguing interplay of PRRSV with monocytic cells

Porcine reproductive and respiratory syndrome virus (PRRSV) is infecting monocytic cells, leading to lysis and functional disturbances. In-depth analysis of its replication in different monocytic cells leads to better insights in the virological, immunological, pathological and clinical outcome. Old-type PRRSV (LV and VR2332) targets differentiated macrophages that are spread all over the body but with higher concentrations in lungs (alveolar, interstitial and intravascular macrophages), endometrium/placenta and lymphoid tissues. This tropism is the result of several viral-cellular protein interactions. Sialoadhesin acts as a binding and internalization receptor. It interacts with sialic acids, present on the glycans of GP5. Upon entry, PRRSV becomes disassembled via a complex cascade of events. First, viral-containing endosomes fuse with other endosomes and proteases become activated by a pH drop. CD163 is crucial during this stage of the replication cycle. Primary replication occurs in tonsils and deeper parts of the respiratory tract. Afterwards, it replicates in internal lymphoid tissues. Because cells die by apoptosis, inflammation is restricted and pathology and clinical signs are moderate (American type>European type). Monocytic cells play a central role in the innate immune response and their destruction during a PRRSV infection may lead to catastrophic clinical signs upon co-infections with pathogens or exposure to toxins. In addition, interaction of PRRSV with sialoadhesin has recently been shown to block phagocytosis. PRRSV only crosses the placenta after 70 days of gestation. The reason for the absence of transplacental spread during earlier gestation can be attributed to (1) the absence of sialoadhesin on placental macrophages in the allantochorion and (2) the presence of efficient defense against PRRSV-infected cells. Microchimerism may be involved in the transplacental crossing of PRRSV during late gestation. Emerging Eastern European (Lena) and Asian (high fever disease) PRRSV strains are behaving differently. They replicate to higher titers, spread more easily, cause more pathology (vascular damage) and disease (fever during 10-14 days upon single infection; fever during 21-28 days with high mortality upon co-infection). With the Lena strain, new insights in the cellular pathogenesis were already obtained. PRRSV(Lena) replicates in hundred times more cells in the respiratory tract. In contrast with old-type PRRSV, it has gained access to a population of large sialoadhesin-negative epithelial and subepithelial monocytic cells with long and multiple cellular filopodia. Morphologically, they resemble mucosal dendritic cells. This new target explains a lot of the changed pathogenesis. High virus titers are produced in the nasal mucosa, facilitating horizontal transmission. A network of connected dendritic cells is as a fisher’s net filtering out attacking pathogens. Destruction of these cells by PRRSV(Lena) opens the fence for invading pathogens. The latter may explain why sepsis is regularly observed in PRRSV(Lena) infected animals.

Jaar van publicatie:2013