Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery.

Hydroxychloroquine (HCQ) is an antimalarial drug also used in treating autoimmune diseases. Its antiviral activity was demonstrated in restricting HIV infection in vitro; however, the clinical implications remain controversial. Infection with dengue virus (DENV) is a global public health problem, and we lack an antiviral drug for DENV. Here, we evaluated the anti-DENV potential of treatment with HCQ. Immunofluorescence assays demonstrated that HCQ could inhibit DENV serotype 1-4 infection in vitro. RT-qPCR analysis of HCQ-treated cells showed induced expression of interferon (IFN)-related antiviral proteins and certain inflammatory cytokines. Mechanistic study suggested that HCQ activated the innate immune signaling pathways of IFN-ß, AP-1, and NFκB. Knocking down mitochondrial antiviral signaling protein (MAVS), inhibiting TANK binding kinase 1 (TBK1)/inhibitor-κB kinase ɛ (IKKɛ), and blocking type I IFN receptor reduced the efficiency of HCQ against DENV-2 infection. Furthermore, HCQ significantly induced cellular production of reactive oxygen species (ROS), which was involved in the host defense system. Suppression of ROS production attenuated the innate immune activation and anti-DENV-2 effect of HCQ. In summary, HCQ triggers the host defense machinery by inducing ROS- and MAVS-mediated innate immune activation against DENV infection and may be a candidate drug for DENV infection.

The impact of systemic lupus erythematosus on women's sexual functioning.

INTRODUCTION: The effect of systemic lupus erythematosus (SLE) on women's sexual functioning has been rarely assessed. AIM: The aim of this study is to evaluate the impact of SLE on women's sexual functioning. METHODS: A total of 302 consecutive female outpatients with SLE were provided with a questionnaire composed of the Female Sexual Function Index (FSFI), questions for sociodemographic characteristics and comorbidities. Similarly, 2,159 hospital female employees were assessed as the control group. In patients, data of SLE duration and Sjögren's syndrome were derived from the chart records and the disease activity was assessed using the SLE Disease Activity Index 2000. MAIN OUTCOME MEASURES: The FSFI scores were compared between the patients and the controls. Correlates of the FSFI scores were determined in the patients. RESULTS: Of 302 eligible patients, 92.4% (279/302) responded, in addition to 73.2% (1,580/2,159) of controls. Ninety-five percent (255/268) of the respondent patients were in no-to-mild SLE disease activity. Among the respondents, 171 (61.3%) patients and 930 (58.9%) controls were sexually active in the previous month, P = 0.446. Of the sexually active patients, 52.5% (85/162) had impaired sexual function (the FSFI total score < 26.55) and so did 47.1% (408/867) of the sexually active controls, P = 0.206. With adjustment of age group, marital status and education level, patients had lower FSFI scores than controls only in the domains of lubrication and pain. Significant risk factors for lower FSFI scores in the patients included persistent activity or flare of SLE, menstrual cycle disturbances, and vascular disease. With further adjustment of other risk factors, only vascular disease remained significant as a risk factor for impaired sexual function (odds ratio = 5.7; 95% confidence interval 1.6-20.1). CONCLUSION: When not in an exacerbation period, the impact of SLE on women's sexual functioning is not great and is related to vascular factors.