TRIM22 IS A NOVEL RESTRICTION FACTOR OF HERPESVIRUSES

The host response to the family of nuclear replicating DNA viruses or the herpesviruses includes the intrinsic, innate and adaptive arms of the immune system. Intrinsic resistance is a constitutively active line of defense against virus infections and members of the Tripartite Motif (TRIM) superfamily of proteins; such as TRIM5 and TRIM19/PML in nuclear domain 10 (ND10) bodies are important restriction factors in this system. Nuclear intrinsic restriction against the prototypical DNA virus, herpes simplex virus 1 (HSV-1) includes interferon-inducible protein 16 (IFI16) and ND10 bodies. However, the viral E3 ubiquitin ligase, ICP0, encoded by wild-type HSV-1, targets these intrinsic immune proteins for degradation. Previous reports on the anti-viral function of TRIM22, the human paralog of the prototypical TRIM5α protein, emphasized its role as a gene of the innate immune system, particularly its expression as a Type I and Type II interferon-stimulated gene and its antiviral function against retroviruses. This study shows that TRIM22 has an additional intrinsic immune role against DNA viruses, using the herpesviruses as an example of a family of DNA viruses. We report that TRIM22 is a novel restriction factor of HSV-1 and limits HSV-1 ICP0-null virus replication. The TRIM22-mediated restriction of HSV-1 occurs after nuclear entry but prior to viral immediate-early gene transcription, by promoting histone occupancy and heterochromatinization to reduce immediate-early viral gene expression. The ICP0-rescued virus evades the TRIM22-specific restriction by a mechanism independent of TRIM22 degradation. We also demonstrate that TRIM22 inhibits other DNA viruses, including representative members of the β- and γ- herpesviruses. These results collectively show that TRIM22 acts in the nucleus, and provide evidence that TRIM22 restricts HSV gene expression by promoting histone occupancy on the viral genes. Furthermore, we identified seven haplotypic variants of TRIM22 and propose that amino acid substitutions in the linker L2 domain and the coiled-coil domain of TRIM22 alter the magnitude of its restriction against the herpesviruses. Together, these results argue for the importance of the TRIM22 gene as a restriction factor against herpesviruses and offer a novel avenue for further investigation on the role of TRIM genes in host genetic variation in herpesviral susceptibility.Medical Science

Postural fall in systolic blood pressure is a useful warning sign in dengue fever [version 2; peer review: 2 approved]

Background Capillary leak is the hallmark of development of severe dengue. A rise in haematocrit has been a major warning sign in WHO guidelines. Postural hypotension, which could reflect the intravascular volume reduction in capillary leak has been noted as warning sign in CDC and Pan American Health Organisation guidelines. We evaluated the diagnostic accuracy of postural hypotension as a marker of development of severe dengue. Methods 150 patients admitted with dengue fever were recruited in this prospective observational study. Diagnostic accuracy of conventional warning signs (abdominal pain, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, increasing hematocrit with decreasing platelets) and postural hypotension was evaluated. Results 23 (15.3%) subjects developed severe dengue. Multiple logistic regression analysis showed that ascites/pleural effusion and postural fall in systolic blood pressure of >10.33% had odds ratio of 5.024(95%CI:1.11 – 22.75) and 11.369 (95% CI:2.27 – 56.87), respectively. Other parameters did not reach statistical significance. Sensitivity and specificity of ascites/pleural effusion were 82.6% and 88.2% for development of severe dengue whereas postural fall in systolic blood pressure had sensitivity and specificity of 87% and 82.7%. Conclusions These findings present a strong case for including postural hypotension as a warning sign in patients with dengue fever, especially in resource limited settings

A Comparative Study on Caprini RAM Vs DOH Tool for Thromboprophylaxis in ICU Setting at Tertiary Care Hospital

The aim of the study was to assess DVT prophylaxis using two models (Caprini RAM & DOH tool) for the prevention of DVT in postoperative or critically ill patients and for better predictability of disease. In this prospective observational study, we compared the Caprini RAM and DOH tool in the ICU setting on 229 patients (140 men and 89 women). 205 patients were considered in the study, out of which 97 had Caprini RAM and 108 had DOH tool. A Prospective, observational comparative study was carried out in a tertiary care hospital for a period of 6 months. Patients were divided into two groups according to the RAM. The data were analyzed using SPSS software and the results were compared using the student t-test. Both GROUP A and GROUP B revealed that the majority of the patients (67.1% & 55.6%) were above 60 years and a large proportion of them required DVT prophylaxis. In GROUP A 93% of forms were complete with 79% accuracy. In GROUP B 83% were complete. The most appropriate prophylaxis received by patients was Enoxaparin sodium 40 mg OD for about 97 (30%) patients and Heparin 5000 IU BD for 108 (30%) based on their Caprini scores and NICE guidelines respectively. The majority of patients in Group A did not require dosage adjustments, but in 20% of cases, it was necessary. Statistical significance was achieved with a p-value less than 0.05. The study demonstrates DOH tool is better than Caprini RAM to be used in hospitals, for risk assessment of VTE in both medical and surgical patients for accuracy and predictability of the prophylaxis. Keywords: DVT, Risk assessment, Caprini RAM, DOH tool, pharmacological and mechanical Prophylaxis