[PMC free article] [PubMed] [Google Scholar] 18. phenotypes correlate with the abilities of these viruses to infect and replicate in macrophages, a feature of Eliglustat tartrate FIPV 79-1146 but not of FECV Eliglustat tartrate 79-1683. To identify the genetic determinants of the FIPV 79-1146 macrophage tropism, we exchanged regions of its genome with the corresponding parts of FECV 79-1683, after which the ability of the FIPV/FECV hybrid viruses to infect macrophages was tested. Thus, we established that Eliglustat tartrate the FIPV spike protein is the determinant for efficient macrophage infection. Interestingly, Eliglustat tartrate this property mapped to the C-terminal domain of the Rabbit polyclonal to Src.This gene is highly similar to the v-src gene of Rous sarcoma virus.This proto-oncogene may play a role in the regulation of embryonic development and cell growth.The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase.Mutations in this gene could be involved in the malignant progression of colon cancer.Two transcript variants encoding the same protein have been found for this gene. protein, implying that the difference in infection efficiency between the two viruses is not determined at the level of receptor usage, which we confirmed by showing that infection by both viruses was equally blocked by antibodies directed against the feline aminopeptidase N receptor. The implications of these findings are discussed. Viruses interact with their hosts in many different ways, giving rise to infections with highly diverse disease outcomes. Most viral infections can be cleared by the immune system with few adverse effects for the host. Many viruses, however, have evolved active mechanisms for bypassing or disarming host defenses, while in other cases the host immune response, in its attempt to clear the pathogen, causes severe immune-mediated damage. Multiple factors, both host and virus derived, determine the nature and severity of such immune pathology. Well-known examples of viruses that can induce severe immune-mediated damage are dengue, hepatitis C, and respiratory syncytial virus, but it is clear that immune-mediated processes also underlie the pathogenesis of coronaviruses, such as the human severe acute respiratory syndrome (SARS) coronavirus and the feline infectious peritonitis virus (FIPV). Coronaviruses are a family of enveloped plus-stranded RNA viruses, members of which occur in many animal species as well as in humans, generally causing respiratory or intestinal infections. Coronaviruses of cats, the feline coronaviruses (FCoVs), come in two biotypes. The most common one is the ubiquitous feline enteric coronavirus (FECV) that can cause a mild to moderate transient enteritis in kittens but which may also pass unnoticed. Often, the virus cannot be cleared, and the infection persists in cells of the intestinal mucosa. In contrast, FIPV occurs more sporadically but is highly virulent and induces a usually fatal immunopathological disease characterized by severe systemic inflammatory damage of serosal membranes and disseminated pyogranulomas (for a review, see reference 7). Recent evidence indicates that the two biotypes are merely virulence variants of the same virus and that FIPV actually originates from FECV by mutation within a persistently infected animal (37). The mutation(s) responsible for the virulence transition has not been identified. It appears that no single mutation within any one gene accounts for the shift, though changes in the viral spike gene and in the group-specific genes and/or were typically observed (37). Attenuation, on the other hand, is readily observed upon passaging of FIPV in vitro in culture cells, a phenomenon associated with loss-of-function mutations in the gene (14). Altogether, the results imply a role for several genes, encoding both structural and nonstructural proteins, in virulence. The transition from FECV to FIPV is accompanied by a remarkable acquisition of macrophage tropism. Whereas FECV replication is primarily restricted to the mature intestinal epithelial cells (27, 28), virulent FIPV strains exhibit a prominent tropism for macrophages (6, 25, 31, 38, 39), infection of which causes a rapid dissemination of the virus throughout the body. FIPV-infected macrophages play a dominant role in bringing about the typical immunopathological damage, as viral antigen can be detected in macrophages in pyogranulomatous lesions in various organs, including liver, spleen, and kidney (26). Moreover, severe T-cell depletion, probably as a result of apoptosis (11), has been observed in lymphoid organs in association with FIPV-positive macrophages. The cause of the T-cell depletion is largely unknown, but the release of proinflammatory cytokines with subsequent cytokine dysregulation has been suggested Eliglustat tartrate to play a critical role (6, 11). It is of note that the worsening of the respiratory symptoms observed in patients infected with SARS-CoV is also associated with severe immunopathological damage induced by stimulated macrophages (23, 30). FIPVs efficiently infect and replicate in cultured primary feline peritoneal macrophages, as illustrated by the highly virulent isolate 79-1146. This is in contrast to FECVs, which do so only poorly (35), as exemplified by the genetically closely related but independently obtained FECV isolate 79-1683. FIPV strain 79-1146 was obtained from a 4-day-old kitten that suffered a neonatal death. The lungs, liver, and spleen showed sites of inflammation from which the coronavirus could.
- Next Mouse cDNA (GenBankTM accession quantity “type”:”entrez-nucleotide”,”attrs”:”text”:”NM_182840″,”term_id”:”599044775″,”term_text”:”NM_182840″NM_182840) contains an open reading framework of 2277 bp and encodes for any protein of 758 amino acids including a signal peptide of 21 residues (Fig
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- This purification/viral inactivation process, based on small volume and disposable equipment, could be ideal for the preparation of hyperimmune IgG from convalescent plasma in infectious outbreaks, as seen currently in West African countries exposed to the Ebola virus [6,40]
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- Isotype-matched F(ab)2 was from Jackson Immuno-Research Laboratories, Inc
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