The importance of myeloperoxidase enzyme activity in the pathogenesis of Crimean-Congo haemorrhagic fever.

Crimean-Congo haemorrhagic fever (CCHF) is a disease with a severe course including acute viral haemorrhagic fever, ecchymosis, thrombocytopenia, hepatic function disorder and high mortality. Myeloperoxidase (MPO) is an enzyme located in neutrophil granulocytes and plays an important role in the destruction of phagocytosed micro-organisms. The aim of this study was to analyse MPO enzyme activity in CCHF cases compared with a control group. A total of 47 randomly selected CCHF patients admitted to the Department of Infectious Diseases of Cumhuriyet University Hospital in Sivas, Turkey, were studied, and as a control group, 41 age- and sex-matched individuals without any systemic disease were included in this study. MPO enzyme activity was measured in plasma and leukocytes for both groups by the ELISA method. MPO plasma and MPO leukocyte values were calculated as 57.62 ± 8.85 and 44.84 ± 9.71 in CCHF patients, and 0.79 ± 0.29 and 0.49 ± 0.11 in the controls, respectively. MPO enzyme activity was statistically significantly higher in patients with CCHF when compared to the control group. In conclusion, MPO enzyme activity is directly related to the activation of phagocytic leukocytes, and increases in both the plasma and leukocytes in CCHF patients. The increase of the MPO enzyme activity in leukocytes due to viral load leads to the destruction of the leukocyte. It is thought that MPO enzyme activity in plasma was higher in CCHF patients due to the destruction of leukocytes. MPO enzyme activity may be important in terms of the prognosis in patients with CCHF; however, more extensive studies are required on this subject.

Oxidative stress in the adult and pediatric patients with Crimean-Congo haemorrhagic fever.

BACKGROUND & OBJECTIVES: Crimean-Congo haemorrhagic fever (CCHF) can be fatal with bleeding, shock and disseminated intravascular coagulopathy (DIC). Although similar genetic strains have been defined, the causes of the clinical differences between the cases are yet to be found. We aimed to demonstrate the balance between oxidant and antioxidant system in CCHF. METHODS: In this study, the patient group consisted of 72 cases with a positive diagnosis of CCHF according to PCR/ELISA outcome among the patients referred to Cumhuriyet University, Medical Faculty in 2010. A total of 74 volunteers who were not having any viral or metabolic disease, non-smokers and age and sex matched with the patients group were enrolled as the control group. Both in the controls and the patients, individuals aged under 16 yr were defined as group 1 and the individuals aged over 16 yr as group 2. The serum samples were stored at -80°C until the study was carried out. All the samples were simultaneously thawed. In these cases, total antioxidant capacity (TAC), total oxidative status (TOS), oxidative stress index (OSI), lipid peroxide (LPO), paraoxonase (PON) and arylesterase were analyzed with the ELISA method. OSI was calculated. RESULTS: Levels of TOS, OSI and LPO were found significantly higher in CCHF patients in both the groups (p <0.05), whereas levels of TAC, PON1 and arylesterase were lower in CCHF patients compared to the controls, but low level of TAC in the group 1 was not statistically significant. INTERPRETATION & CONCLUSION: Our study demonstrated increased oxidative stress in CCHF patients in both groups 1 and 2. In order to prevent tissue damage which might be developed due to the oxidative stress in CCHF patients, further comprehensive studies should be conducted to define whether the adding antioxidants to the treatment would be helpful or not.

Arterivirus and nairovirus ovarian tumor domain-containing Deubiquitinases target activated RIG-I to control innate immune signaling.

The innate immune response constitutes the first line of defense against viral infection and is extensively regulated through ubiquitination. The removal of ubiquitin from innate immunity signaling factors by deubiquitinating enzymes (DUBs) therefore provides a potential opportunity for viruses to evade this host defense system. It was previously found that specific proteases encoded by the unrelated arteri- and nairoviruses resemble the ovarian tumor domain-containing (OTU) family of DUBs. In arteriviruses, this domain has been characterized before as a papain-like protease (PLP2) that is also involved in replicase polyprotein processing. In nairoviruses, the DUB resides in the polymerase protein but is not essential for RNA replication. Using both in vitro and cell-based assays, we now show that PLP2 DUB activity is conserved in all members of the arterivirus family and that both arteri- and nairovirus DUBs inhibit RIG-I-mediated innate immune signaling when overexpressed. The potential relevance of RIG-I-like receptor (RLR) signaling for the innate immune response against arterivirus infection is supported by our finding that in mouse embryonic fibroblasts, the production of beta interferon primarily depends on the recognition of arterivirus RNA by the pattern-recognition receptor MDA5. Interestingly, we also found that both arteri- and nairovirus DUBs inhibit RIG-I ubiquitination upon overexpression, suggesting that both MDA5 and RIG-I have a role in countering infection by arteriviruses. Taken together, our results support the hypothesis that arteri- and nairoviruses employ their deubiquitinating potential to inactivate cellular proteins involved in RLR-mediated innate immune signaling, as exemplified by the deubiquitination of RIG-I.

Serum chitotriosidase enzyme activity in patients with Crimean-Congo hemorrhagic fever.

BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a public health problem in many countries. Chitotriosidase (ChT) is an enzyme secreted by activated macrophages that catalyzes the hydrolysis of chitin and chitin-like substrates. The goal of this study was to assess the relationship between serum ChT activity and mortality. METHODS: ChT activities on the first day of hospitalization were analyzed in serum from 46 patients with CCHF and 36 healthy controls. Serum ChT activities and other clinical and laboratory parameters for patients with non-fatal and fatal CCHF were compared. RESULTS: The median ChT activity was increased in all patients with CCHF [189.9 (134.8-246.6) nmol/mL/h]. The median ChT activity in the non-fatal CCHF group [220.2 (180.6-290.1) nmol/mL/h] was higher compared with the fatal CCHF group [29.2 (16.5-45.7) nmol/mL/h] (p<0.001). In univariate analysis, platelet count, lactate dehydrogenase (LDH), and activated partial thromboplastin time were associated with mortality. CONCLUSIONS: This is the first study investigating the association of serum ChT enzyme activity with mortality from CCHF. This study suggested that relatively low ChT enzyme activities may be a prognostic marker in patients with CCHF.