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Spring viremia of carp virus (SVCV) is a severe infectious pathogen that causes high rates of mortality in cyprinids and other fish species. Despite numerous investigations of SVCV infection, the underlying molecular mechanisms remain poorly understood. In this study, we found that the SVCV matrix protein (SVCV-M) played an inhibitory role in the host interferon (IFN) response by targeting the MAVS/TRAF3 signaling axis, thereby uncovering a previously unrecognized mechanism of SVCV escape from host innate antiviral immunity. Mechanistically, SVCV-M was located at the mitochondria independent of MAVS, which allowed SVCV-M to build an arena for competition with the MAVS platform. A microscale thermophoresis assay showed that SVCV-M had a high affinity for TRAF3, as indicated by a lower equilibrium dissociation constant (KD) value than that of MAVS with TRAF3. Therefore, the association of MAVS with TRAF3 was competitively impaired by SVCV-M in a dose-dependent manner. Accordingly, SVCV-M showed a potent ability to inhibit the K63-linked polyubiquitination of TRAF3. This inhibition was accompanied by the impairment of the IFN response, as shown by the marked decline in IFN-w 1-promoter (pro) luciferase reporter activity. By constructing truncated TRAF3 and SVCV-M proteins, the RING finger, zinc finger, and coiled-coil domains of TRAF3 and the hydrophobic-pocket-like structure formed by the a2-, a3-, and a4-helices of SVCV-M may be the major target and antagonistic modules responsible for the protein-protein interaction between the TRAF3 and SVCV-M proteins. These findings highlighted the intervention of SVCV-M in host innate immunity, thereby providing new insights into the extensive participation of viral matrix proteins in multiple biological activities. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the correlation between cystathionine β-synthase (CBS) T833C polymorphisms and primary hypertension. A case-control study was conducted by genotyping the representative variation in 545 hypertensive individuals (aged 49.23±7.56 years) and 500 normotensive individuals (aged 49.90±10.01 years). The T833C genetic polymorphisms of the CBS enzyme were detected in all subjects by amplification refractory mutation system polymerase chain reaction (PCR) analysis. The CBS T833C polymorphism was successfully genotyped in the general population with a sample size of 1,045 (545+500) individuals. The genotypic and allelic frequency distributions of the CBS T833C polymorphism were not significantly different between the hypertensive and normotensive groups (P>0.05). The CC genotype was significantly different (P<0.05) from the CT and TT genotypes in terms of body mass index (BMI), and the levels of triglycerides (TG) and homocysteine (Hcy). Multiple logistic regression analysis revealed that BMI, total cholesterol (TC) level, smoking, plasma Hcy level and a family history of hypertension were the independent risk factors for hypertension in the population studied. The results indicate that the level of plasma Hcy was a risk factor for hypertension in the population studied. However, the mutation of the CBS T833C gene was not concluded to be an important hereditary factor for influencing the level of plasma Hcy. [ABSTRACT FROM AUTHOR]