ABSTRACT
Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.
Subject(s)
Antigens, CD , Antigens, Differentiation, Myelomonocytic , Point Mutation , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Receptors, Cell Surface , Animals , Swine , Porcine Reproductive and Respiratory Syndrome/genetics , Porcine Reproductive and Respiratory Syndrome/virology , Porcine respiratory and reproductive syndrome virus/physiology , Porcine respiratory and reproductive syndrome virus/genetics , Antigens, Differentiation, Myelomonocytic/genetics , Antigens, Differentiation, Myelomonocytic/metabolism , Antigens, CD/genetics , Antigens, CD/metabolism , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism , Animals, Genetically Modified/genetics , Cell LineABSTRACT
The flux of matter, energy and nutrients across ecosystems, i.e., resource subsidy, is a fundamental attribute of ecosystems, as well as one of basic research questions in ecology. Common subsidies include leaf litter and terrestrial insects that fall into waters, the adults of aquatic insects, spawning salmon. The allocthonous input of resource subsidy can influence individual organisms, populations, communities, biodiversity and ecosystem functioning, such as enhancing individual growth, increasing species abundance and diversity, affecting community structure, enhancing secondary productivity, influencing food-chain length and food web. Due to increased human impacts on environments, especially at aspects of land use, climate change and invasive species, the influence of anthropogenic disturbance on cross-ecosystem resource subsidies will be intensified at both spacial and temporary scales, so that ecosystems will face severer threats. Accordingly, future ecological researches in this field should emphasize the following aspects: impacts of single and multiple stressors on subsidies and ecosystems, implementation of dynamic resource subsidies on ecosystem restoration and management, the dark sides of subsidy relating with pollutants, and basic ecological research on cross-ecosystem resource subsidy in tropics and sub-tropics, as well in China.
