Upon virus infection, the cell mounts an innate type I interferon (IFN) response to limit the spread. This response is orchestrated by the constitutively expressed IFN regulatory factor (IRF)-3 protein, which becomes post-translationally activated. Although the activation events are understood in detail, the negative regulation of this innate response is less well understood. Many viruses, including Kaposi sarcoma-associated herpesvirus (KSHV), have evolved defense strategies against this IFN response. Thus, KSHV encodes a viral IRF (vIRF)-2 protein, sharing homology with cellular IRFs and is a known inhibitor of the innate IFN response. Here, we show that vIRF-2 mediates IRF-3 inactivation by a mechanism involving caspase-3, although vIRF-2 itself is not pro-apoptotic. Importantly, we also show that caspase-3 participates in normal IRF-3 turnover in the absence of vIRF-2, during the antiviral response induced by poly(I:C) transfection. These data provide unprecedented insight into negative regulation of IRF-3 following activation of the type I IFN antiviral response and the mechanism by which KSHV vIRF-2 inhibits this innate response.
BackgroundThere is limited data in Ghana on the epidemiology of HPV and cervical neoplasia and their associations with HIV. This study aimed to compare among HIV-1 seropositive and HIV-seronegative Ghanaian women: (1) the prevalence, genotype distribution and risk factors associated with cervical HPV infection; and (2) the prevalence and risk factors associated with abnormal cervical cytology.MethodsA comparative frequency-matched study was conducted in a systematic sample of women aged ≥18 years attending HIV and general outpatient clinics in Cape Coast Teaching Hospital, Ghana. Participants were interviewed and cervical samples collected for HPV genotyping (Seegene Anyplex-II HPV28) and cytological testing.ResultsOverall, 333 women were recruited, 163 HIV-1 seropositive and 170 HIV-seronegative women of mean age 43.8 years (SD ±9.4)) and 44.3 years (SD ±12.8), respectively. The prevalence of 14 high-risk (hr) HPV genotypes was higher among HIV-1 seropositive women (65.6% vs. 30.2%, P < 0.0001), as was proportion with multiple hr.-HPV infections (60.6% vs. 21.3%, P < 0.0001). HPV35 was the most prevalent hr.-HPV genotype in both groups (11.9% and 5.3%). The main factors associated with hr.-HPV infection were age for HIV-positive women and circumcision status of main sexual partner for both HIV-negative and positive women.Abnormal cervical cytology prevalence was higher among HIV-1 seropositive women (any SIL: 14.1% vs. 1.2%, P < 0.0001; low-grade SIL [LSIL]: 4.9% vs. 0.6%, P = 0.02; high-grade SIL: 1.8% vs. 0%, P = 0.07). Among HIV-1 seropositive women, number of pregnancies and CD4+ cell count were associated with LSIL+ cytology. There was strong association between LSIL+ abnormalities and HPV35 (aOR = 4.7, 95%CI: 1.3–17.7, P = 0.02).ConclusionsHIV-1 infected women bear significant burden of HPV infection and related disease. Prevention and screening programmes should be specifically deployed for this population in Ghana.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3682-x) contains supplementary material, which is available to authorized users.
IntroductionBlood borne viral hepatitis transmission still ranges between 4-20% in many Ghanaian communities. Hepatocellular carcinoma (HCC) also called liver cancer is reported as the leading cause of cancer mortality among males in Ghana. We studied the knowledge and risk factors associated with barbers’ occupation in the transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV).MethodsA randomized cross-sectional survey of 200 barbershops was conducted in Kumasi between January and August 2013. Barbershops, which operated continuously for more than 8 months, were selected for the study. Structured questionnaires were administered to the study participants. Data was entered and analysed in Microsoft Excel spread sheet and SPSS v12. The percentage value of each question was calculated.ResultsAll the barbers involved in this study used a new razor blade on every client and claimed to sterilize the hair trimmers after use on every client. The methods of sterilization; 46.5% of the barbers used the ultraviolet radiation sterilizer cabinet, 29% used 70% alcohol and 23% used antiseptic solutions. More than thirty-six percent (36.5%) and 5% of the barbers had heard of HBV and HCV respectively. Only 7% and none knew the route of transmission of HBV and HCV respectively, whereas 7% knew sharing razor blade or hair trimmer could transmit both HBV and HCV. More so, 2% knew HBV and HCV could cause cancer and 2% had received the HBV vaccine. The majority of barbers (63%) had education up to the junior secondary school level. None of the barbers used a new apron nor washed their hands after work on each client.ConclusionAwareness of barbers about HBV or HCV and job-related factors contributing to spread of infections was very poor among the vast majority of the barbers studied. Thus, giving training for the barbers is required toward prevention of blood- borne infections associated to their profession.
Disclosure of potential conflict of interest: R. Newton's institution received a grant from AstraZeneca for other works and he personally received travel expenses from AstraZeneca. The rest of the authors declare that they have no relevant conflicts of interest.
Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes four viral interferon regulatory factors (vIRF-1–4). We investigated the mechanism and consequences of vIRF-2-mediated inhibition of interferon-response element signalling following type I interferon (IFN) induction. Western blot and electrophoretic mobility-shift assays identified the interferon-stimulated gene factor-3 (ISGF-3) components STAT1 and IRF-9 as the proximal targets of vIRF-2 activity. The biological significance of vIRF-2 inhibition of ISGF-3 was demonstrated by vIRF-2-mediated rescue of the replication of the IFN-sensitive virus encephalomyocarditis virus. This study provides both a mechanism and evidence for KSHV vIRF-2-mediated suppression of the consequences of type 1 IFN-induced signalling.
BackgroundHepatitis B virus infection (HBV) is one of the most widespread, chronic viral infections in sub-Saharan Africa, and parts of South America. Therefore, efforts are being made to implement strategies aimed at reducing the incidence of hepatitis B viral infections. One route of HBV transmission is through unsafe blood transfusion, which could occur from the use of less sensitive laboratory diagnostic kits. Information on the sensitivity and specificity of these kits is however limited in many developing countries. This study was therefore performed to describe the prevalence of HBV infections and also to evaluate the performance of five rapid immunochromatographic kits commonly used in Ghana.MethodsA cross-sectional study was designed to describe the prevalence of HBsAg infection and also evaluate the performance of rapid kits used for screening hepatitis B in the northern part of Ghana.ResultsA total of 164 prospective blood donors were enrolled in this study from January 2012 to December 2013. The overall true prevalence of HBsAg was 14.6 (95% CI = 9.6 – 21.0). There was no significant association between transmission related factors and HBV infection. The specificities of all five rapid kits were above 97%, however the sensitivities and Youden’s indexes were below 60%. A comparison of the reported kit sensitivities to those generated by this study showed significant difference with the study results being lower than the ones reported in the kit literature.ConclusionOur study has shown that rapid HBsAg kits on the Ghanaian markets may not be helpful for screening blood donor samples. We therefore recommend the use of commercially available enzyme linked immunosorbent assays.
Background The study assessed the hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infection paradigm among the human immunodeficiency virus (HIV) infected patients attending a tertiary hospital in Ghana. Also, the immunological and virological characterisation of these viruses, prior to antiretroviral therapy (ART) initiation was investigated. Method A total of 400 HIV infected (HIV type-1) treatment naïve subjects ≥18 years were enrolled and tested for HBsAg and anti-HCV. Hepatitis B virus serological profile was performed on samples that were HBV positive. CD4+ T-cell count and HIV-1 RNA viral loads were determined using BD FacsCalibur analyzer (USA) and COBAS AmpliPrep/COBAS TaqMan Analyzer (USA) respectively. Results The overall prevalence of HBV/HCV co-infection among the HIV-1 patients was 18.0%. The prevalence of HIV-HBV and HIV-HCV co-infections were 12.5% and 5.5% respectively. The prevalence of active viral hepatitis (HBeAg-positive) among HIV-HBV co-infected patients was 40%. None of the patients had anti-HBc IgM. HIV-HBV co-infection was associated with lower CD4+ T-cell count as well as higher HIV-1 viral load compared to both HIV mono- infection and HIV-HCV co- infection ( p <0.05) respectively. HBeAg positivity was associated with severe immunosuppression and higher HIV viral load. Patients aged 18–33 years [aOR = 9.66(1.17–79.61); p = 0.035], male gender [aOR = 2.74(1.15–6.51); p = 0.023], primary education [aOR = 9.60(1.21–76.08); p = 0.032], secondary education [aOR = 14.67(1.82–118.08); p = 0.012] and being single [aOR = 2.88(1.12–7.39); p = 0.028] were independent risk factors of HIV-HBV co-infections but not HIV-HCV co-infections. Conclusion The present study highlights the predominance of HBV exposure among the HIV infected patients in Ghana. HBV coinfection was associated with severe immunosuppression and higher HIV-1 viral load.
Hepatitis B viral infection is an important clinical problem due to its worldwide distribution and potential of adverse sequelae, including hepatocellular carcinoma (HCC). We studied the prevalence of hepatitis B virus ‘e’ antigen (HBeAg) among individuals determined to be hepatitis B virus (HBV) surface antigen-positive and analyzed the gender/age category associated with more active HBV infection and whether alteration in the levels of alanine aminotransferase could be associated with HBeAg positivity. A total of 150 prospective blood donors who tested positive for hepatitis B surface antigen (HBsAg) at the blood transfusion center of the Komfo Anokye Teaching Hosptital (KATH), Kumasi were randomly selected for the study. The serum samples were further tested for HBsAg and HBeAg using a lateral flow immunochromatographic assay. Twenty (20) individuals were found to be HBeAg-positive giving an overall prevalence of 13.3%, of which 18 (15.5%) were males and 2 (5.9%) were females. Our results also revealed that the prevalence of HBeAg was higher in patients between the age group of 10-20 years and appeared to decrease with increase in age. There was no statistical difference between the HBeAg positive and negative individuals with respect to alanine aminotransferase (ALT) levels. We show for the first time that approximately 1/10 of HBV-infected individuals are HBeAg positive in the Ashanti Region of Ghana, suggestive of active viral replication and liver-cell infectivity thereby contributing to an increased HBV-transmission pool within the Ghanaian population.
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