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Background: Herpes Simplex Virus Type 2 (HSV 2) is one of the most common sexually transmitted infections (STIs) worldwide. HSV 2 infection is a risk factor for the acquisition and transmission of other STIs. Aim: The aim of this study is to determine prevalence and predictors of HSV 2 infection in Durban, South Africa by using available data that has not been previously analysed for the purpose of adding scientific evidence to the existing body of knowledge relating to HSV 2. Method: The study involves secondary analyses of data collected as a prospective study which enrolled women who participated in a clinical trial. A total of 3472 sexually active women were screened in the primary study from two clinics in Durban. All consenting participants were tested for HIV, HSV 2, Trichomonas vaginalis (TV), Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) infection. Results: There were 2532 women who had HSV 2 giving a prevalence of 73%. Of these, 53% also tested positive for HIV infection. In univariate analysis, co-infection with HIV was strongly associated with HSV2 (Odds Ratio (OR): 7.4, 95% Confidence Interval (CI): 6.0, 9.1, p<0.001). There was also an association between other STIs, such as CT, NG and syphilis and HSV 2, although only NG was significantly associated with prevalent of HSV 2 (OR: 2.3, 95% CI: 1.3, 4.1, p=0.005). Women older than 25 years of age more likely to have HSV 2 (OR: 2.4, 95% CI: 2.0,2.8, p<0.001). A risk of being infected with HSV 2 increased with the number of reported lifetime sexual partners Those with two and three or more were 2,5 and 4.6 times more likely to have HSV2 respectively (OR: 2.5, 95% CI: 2.1,3.1, p<0.001 and OR: 4.6, 95% CI: 3.8, 5.6, p<0.001 respectively). Women who had less than high school education were also found to have higher risk for HSV 2. Conclusion: The secondary analysis showed a high prevalence of HSV 2 infection and a strong association of HSV 2 and HIV. A significant association of HSV 2 was noted in women having more than two sex partners and lower high school education. Therefore, it is recommended that screening for HSV 2 among high risk populations be incorporated into the STI screening and treatment packages. / Prevalence and risk factors associated with HSV 2 / Herpes Simplex Virus Type 2 / HSV 2 / Department of Health Studies / M. (Public health)

Background: Herpes Simplex Virus Type 2 (HSV 2) is one of the most common sexually transmitted infections (STIs) worldwide. HSV 2 infection is a risk factor for the acquisition and transmission of other STIs. Aim: The aim of this study is to determine prevalence and predictors of HSV 2 infection in Durban, South Africa by using available data that has not been previously analysed for the purpose of adding scientific evidence to the existing body of knowledge relating to HSV 2. Method: The study involves secondary analyses of data collected as a prospective study which enrolled women who participated in a clinical trial. A total of 3472 sexually active women were screened in the primary study from two clinics in Durban. All consenting participants were tested for HIV, HSV 2, Trichomonas vaginalis (TV), Neisseria gonorrhoea (NG) and Chlamydia trachomatis (CT) infection. Results: There were 2532 women who had HSV 2 giving a prevalence of 73%. Of these, 53% also tested positive for HIV infection. In univariate analysis, co-infection with HIV was strongly associated with HSV2 (Odds Ratio (OR): 7.4, 95% Confidence Interval (CI): 6.0, 9.1, p<0.001). There was also an association between other STIs, such as CT, NG and syphilis and HSV 2, although only NG was significantly associated with prevalent of HSV 2 (OR: 2.3, 95% CI: 1.3, 4.1, p=0.005). Women older than 25 years of age more likely to have HSV 2 (OR: 2.4, 95% CI: 2.0,2.8, p<0.001). A risk of being infected with HSV 2 increased with the number of reported lifetime sexual partners Those with two and three or more were 2,5 and 4.6 times more likely to have HSV2 respectively (OR: 2.5, 95% CI: 2.1,3.1, p<0.001 and OR: 4.6, 95% CI: 3.8, 5.6, p<0.001 respectively). Women who had less than high school education were also found to have higher risk for HSV 2. Conclusion: The secondary analysis showed a high prevalence of HSV 2 infection and a strong association of HSV 2 and HIV. A significant association of HSV 2 was noted in women having more than two sex partners and lower high school education. Therefore, it is recommended that screening for HSV 2 among high risk populations be incorporated into the STI screening and treatment packages. / Prevalence and risk factors associated with HSV 2 / Herpes Simplex Virus Type 2 / HSV 2 / Department of Health Studies / M. (Public health)

Le criblage par siRNA de 49 protéines de l'hôte qui sont incorporées dans les particules matures du virus herpès simplex de type 1 (VHS-1) a révélé l'importance d'au moins 15 d’entre elle pour infectivité du virus (Stegen, C et al. 2013). Parmi celle-ci figure la protéine humaine DDX3X, qui est une ARN hélicase ATP-dépendante. Cette protéine multifonctionnelle participe à différents stages de l'expression génique, tels que la transcription, la maturation et le transport d'ARNm ainsi que la traduction. DDX3X est impliquée dans la réplication de plusieurs virus tels que le Virus de l’immunodéficience humaine de type 1 (VIH-1), l'hépatite B (VHB), le virus de la vaccine (VACV) et le virus de l'hépatite C (VHC). Le rôle exact de DDX3X dans le cycle de réplication du VHS-1 est toutefois inconnu. Ce mémoire consiste en l’étude détaillée de l'interaction de DDX3X avec le virus. De manière surprenante, tant l’inhibition que la surexpression de DDX3X réduit de manière significative l'infectivité du VHS-1. Fait intéressant, lorsque nous avons restauré la déplétion de DDX3X par une construction résistante aux ARNi utilisés, le virus pouvait de nouveau infecter les cellules efficacement, indiquant que le virus est sensible aux quantités de cette protéine de son hôte. Nos résultats indiquent de plus que le virus modifie la localisation de DDX3X et cause son agrégation tôt dès les premiers temps de l'infection. Cependant, le virus ne modifie pas les niveaux cellulaires de DDX3X dans deux des trois lignées cellulaires examinées. Nous avons également pu établir que cette protéine n'a pas d'effet sur l'entrée du VHS-1, suggérant qu’elle agit à un stade ultérieure de l’infection. En examinant cette relation plus en détail, nos résultats ont démontré que l’inhibition ou la surexpression de DDX3X inhibent toutes deux la production de nouvelles particules virales en réduisant l'expression des diverses classes cinétiques des protéines virales et ce au niveau de leur transcription. Malgré le rôle connu DDX3X dans la stimulation de la réponse immunitaire innée et la production d’interférons de type I, l’impact de DDX3X sur la réplication du VHS-1 est ici indépendante de cette fonction. Ces travaux démontrent donc une nouvelle voie d’action de DDX3X sur les virus en agissant directement sur la transcription de gènes viraux et la réplication du génome d’un virus à ADN. En comprenant mieux cette interactions hôtepathogène, il est maintenant envisageable de concevoir des nouvelles approches thérapeutiques contre ce virus. / siRNA screening of 49 host proteins that are known to be incorporated in the mature virions of herpes simplex virus type 1 (HSV-1) revealed the importance of at least 15 cellular proteins for viral infectivity (Stegen, C et al. 2013). Among these, was the human protein DDX3X, a DEAD-box ATP-dependent RNA helicase. This multifunctional protein participates in different stages of gene expression such as mRNA transcription, maturation, mRNA export and translation. DDX3X has been shown to be involved in the replication of several viruses such as human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) vaccinia virus (VACV) and hepatitis C virus (HCV). The exact role of DDX3X in HSV-1 replication cycle is not known. Here we sought to find the detailed interaction between DDX3X with HSV-1. Surprisingly, the down-regulation as well as overexpression of DDX3X, significantly reduced the infectivity of HSV-1, indicating that the virus is sensitive to the precise levels of DDX3X. Accordingly, when we rescued DDX3X back to its normal cellular levels by sequential transfection of DDX3X siRNA and siRNA resistant DDX3X plasmid, the virus was able to infect cells efficiently compare to wild-type conditions. Furthermore, the virus changes the localization of DDX3X and causes its aggregation at early times in the infection. However, the virus does not change the cellular levels of DDX3X in at least two of three different cell lines tested. Using a luciferase assay we were able to establish that this protein has no effect on the entry of HSV-1. In fact, depleting or overexpressing DDX3X impaired the production on newly assembled viral particles by blocking the expression of all classes of viral proteins at the transcription level. Despite the known role of DDX3X in the stimulation of innate immune response and interferon type I production, DDX3X appears to act on HSV-1 replication independently of this pathway. This highlights a novel route of action of DDX3X by acting at the transcription level and the consequent genome replication of a DNA virus. By better understanding such pathogen interactions, it might now be possible to design novel therapeutic approaches.

Le virus de l’Herpès simplex de type 1 (HSV-1) est le pathogène humain responsable des lésions herpétiques labiales, plus communément appelé « feux sauvages ». Annuellement, il est responsable de plusieurs cas d’encéphalites et d’infections de l’appareil visuel qui sont la principale cause de cécité en Amérique du Nord. Bien qu’il existe quelques traitements antiviraux, aucun vaccin ou médicament ne permet de prévenir ou de guérir les infections causées par ce virus. Aujourd’hui, les infections produites par l’HSV-1 sont présentes partout sur la planète. Récemment, une étude en protéomique effectuée sur les virus matures extracellulaires a permis d’identifier la présence d’ubiquitines libres et d’enzymes reliées à la machinerie d’ubiquitination dans le virus. De plus, le virus exploite cette machinerie au cours de l’infection. Il est connu que certaines protéines virales sont ubiquitinées durant une infection et que le virus imite même certaines enzymes d’ubiquitination. Nous avons donc entrepris des recherches afin d’identifier des protéines virales ubiquitinées qui pourraient être présentes dans les virus matures ainsi que leurs rôles potentiels. La protéine majeure de la capside, VP5, un constituant très important du virus, a été identifiée. Nos recherches nous ont permis de caractériser le type d’ubiquitination, une monoubiquitination sur les lysines K810 et/ou K1275 de VP5. Le rôle que pourrait jouer l’ubiquitination de VP5 dans le cycle de réplication virale et dans les virus matures n’est toutefois pas encore connu. / Herpes simplex virus type 1 (HSV-1) is the human pathogen responsible for herpetic lesion such as cold sores. On a yearly basis, it is responsible for many cases of encephalitis and infections of the eye that are the most common cause of blindness in North America. Antiviral treatments exist, but no vaccines or drugs are able to prevent or cure the diseases caused by this virus. Today, infections caused by HSV-1 are present all around the world. Recently a proteomics approach was used to study mature extracellular viruses. This study highlighted the presence in the virus of free ubiquitin and ubiquitin related enzymes. Furthermore, the virus exploits this machinery during the course of infection. Also, it is known that certain virally encoded proteins are ubiquitinated and that the virus mimics some ubiquitin related enzymes. Our researches focused on identifying ubiquitinated viral proteins that could be present in mature extracellular viruses and their potential roles. The major capsid protein, VP5, an important virus component, was identified. We characterised the type of ubiquitination, a monoubiquitination of lysine K810 and/or K1275 of VP5. The role that could play the ubiquitination of VP5 in the viral cell cycle and in mature virions has yet to be identified.

Zhu Wen. / "May 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 217-249). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Background: The Division of Global HIV/AIDS at the Centers for Disease Control and Prevention (CDC) is working on a public health evaluation (PHE) in the eastern districts of Botswana. This PHE aims to evaluate the effectiveness of Project AIM, a group-level intervention designed to reduce HIV risk behaviors in youth ages 11 to 14, when combined with the regular Botswana Skills for Life Curriculum, a standard HIV prevention education curriculum in Botswana schools. In order to evaluate Project AIM, a self-report survey and a biological testing for herpes simplex virus type 2 (HSV-2) will be conducted. Methodology: Based on studies done on the psychosocial impact of HSV-2 diagnosis on asymptomatic individuals in the USA, the literature recommends providing pre and post counseling and education to individuals testing for genital herpes to help cope and diminish the psychosocial impact of the diagnosis. In order to prepare Botswana’s clinics and schools participating in the PHE to provide the support for newly diagnosed adolescents with HSV-2, guidance materials were developed for health care practitioners and school guidance teachers. Materials were created using Information Mapping technique to analyze, organize, and present the information, and the Microsoft Office Flesch Kinkade Grade Level (FK) tool to assess the readability levels of the materials. Results: Guidance materials were prepared using the 7±2 theoretical limit of human short-term memory information mapping rule, and the FK grade levels of 6.0 to 8.0 recommended readability scores. Guidance materials included information regarding HSV-2 symptoms, treatment, and prevention. They also included information on the PHE study, youth friendly health services, counseling and education, clinic referrals and contact information. Conclusions: The development of guidance materials for schools and clinic participants of the CDC PHE in Botswana will provide health practitioners and school guidance teachers with accurate HSV-2 information to counsel and educate student participants in this research study. The guidance materials should help students cope with potential psychosocial disorders associated with pre and post diagnosis of HSV-2.

Thesis (Ph. D.)--University of Missouri--Columbia, 2003. / Typescript. Vita. Includes bibliographical references (leaves 139-154).

Le virus de l’Herpès simplex de type 1 (HSV-1) est le pathogène humain responsable des lésions herpétiques labiales, plus communément appelé « feux sauvages ». Annuellement, il est responsable de plusieurs cas d’encéphalites et d’infections de l’appareil visuel qui sont la principale cause de cécité en Amérique du Nord. Bien qu’il existe quelques traitements antiviraux, aucun vaccin ou médicament ne permet de prévenir ou de guérir les infections causées par ce virus. Aujourd’hui, les infections produites par l’HSV-1 sont présentes partout sur la planète. Récemment, une étude en protéomique effectuée sur les virus matures extracellulaires a permis d’identifier la présence d’ubiquitines libres et d’enzymes reliées à la machinerie d’ubiquitination dans le virus. De plus, le virus exploite cette machinerie au cours de l’infection. Il est connu que certaines protéines virales sont ubiquitinées durant une infection et que le virus imite même certaines enzymes d’ubiquitination. Nous avons donc entrepris des recherches afin d’identifier des protéines virales ubiquitinées qui pourraient être présentes dans les virus matures ainsi que leurs rôles potentiels. La protéine majeure de la capside, VP5, un constituant très important du virus, a été identifiée. Nos recherches nous ont permis de caractériser le type d’ubiquitination, une monoubiquitination sur les lysines K810 et/ou K1275 de VP5. Le rôle que pourrait jouer l’ubiquitination de VP5 dans le cycle de réplication virale et dans les virus matures n’est toutefois pas encore connu. / Herpes simplex virus type 1 (HSV-1) is the human pathogen responsible for herpetic lesion such as cold sores. On a yearly basis, it is responsible for many cases of encephalitis and infections of the eye that are the most common cause of blindness in North America. Antiviral treatments exist, but no vaccines or drugs are able to prevent or cure the diseases caused by this virus. Today, infections caused by HSV-1 are present all around the world. Recently a proteomics approach was used to study mature extracellular viruses. This study highlighted the presence in the virus of free ubiquitin and ubiquitin related enzymes. Furthermore, the virus exploits this machinery during the course of infection. Also, it is known that certain virally encoded proteins are ubiquitinated and that the virus mimics some ubiquitin related enzymes. Our researches focused on identifying ubiquitinated viral proteins that could be present in mature extracellular viruses and their potential roles. The major capsid protein, VP5, an important virus component, was identified. We characterised the type of ubiquitination, a monoubiquitination of lysine K810 and/or K1275 of VP5. The role that could play the ubiquitination of VP5 in the viral cell cycle and in mature virions has yet to be identified.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / Este trabalho teve como objetivos caracterizar fÃsico-quÃmica e estruturalmente polissacarÃdeos obtidos de folhas de Aloe barbadensis e avaliar suas atividades antiviral, anti-hemorrÃgica e prÃ-coagulante e possÃveis sinais de toxicidade. Foi realizada extraÃÃo aquosa de polissacarÃdeos totais (PT) de A. barbadensis, seguido de precipitaÃÃo por etanol e remoÃÃo dos contaminantes proteicos com TCA. A cromatografia em DEAE-celulose foi eficiente no fracionamento dos PT, onde foram obtidas as fraÃÃes PI e PII. A caracterizaÃÃo fÃsico-quÃmica mostrou que a fraÃÃo PI à composta por manose (78,4%), glucose (7,3%), galactose (2,1%), fucose (2,8%) e Ãcidos urÃnicos (10,0%), e isenta de grupos Ãster sulfato. Enquanto, a fraÃÃo PII à constituÃda por manose (39,2%), glucose (22,2%), galactose (26,3%), arabinose (3,8%), xilose (1,1%), Ãcidos urÃnicos (8,0%) e grupos Ãster sulfato (12,0%). Na revelaÃÃo das bandas polissacarÃdicas da fraÃÃo PII, obtidas por PAGE e gel de agarose corados com stainsall foi constatado a presenÃa de duas bandas que apresentaram diferentes coloraÃÃes, roxa e ciana, correspondentes a presenÃa de grupos sulfato e carboxilados, respectivamente. Na anÃlise estrutural das fraÃÃes PI e PII, por espectroscopia no IR, foi demonstrado que a fraÃÃo PI apresenta unidades monossacarÃdicas de Ã-manose O-acetiladas (812,2 e 960 onda.cm-1) e Ãcidos urÃnicos neutros (1738 onda.cm-1) em sua estrutura. Diferentemente, a fraÃÃo PII, mostrou-se ser constituÃda por unidades monossacarÃdicas de manose (1014,7 onda.cm-1), galactose (1078,2 onda.cm-1), Ãcidos urÃnicos carregados negativamente (1635 onda.cm-1) e Ãster sulfato (1329,5 e 1260,9 onda.cm-1). Na avaliaÃÃo estrutural da fraÃÃo PII por RMN foi comprovado à presenÃa do grupo Ãster sulfato. Em relaÃÃo Ãs atividades biolÃgicas, o teste de citotoxicidade mostrou que os PT e as fraÃÃes PI e PII nÃo apresentaram toxicidade para a maioria das cÃlulas testadas e nÃo foram eficientes na inibiÃÃo de vÃrus nÃo envelopados Ad-19 e Ad-41. No entanto, os PT e a fraÃÃo PI foram capazes de inibir a infecÃÃo causada por HSV-1 e HSV-2. Em ensaios com metapneumovÃrus (HMPV), a fraÃÃo PII apresentou atividade antiviral superior à ribavirina. Embora os PT e as fraÃÃes PI e PII nÃo terem apresentado atividade contra dengue vÃrus sorotipo 1 (DENV-1), os PT puderam inibir a hemorragia em ratos, diminuindo o tempo de sangramento e o tempo de protrombina. Os PT nÃo apresentaram toxicidade em camundongos, mas aumentaram o tamanho do baÃo e o nÃmero de plaquetas sanguÃneas. Pode ser concluÃdo que extratos foliares de A. barbadensis podem apresentar polissacarÃdeos neutros ou carregados negativamente por grupos carboxilados/sulfatados. Em adiÃÃo, alÃm de apresentar atividade inibitÃria contra os vÃrus HSV-1, HSV-2 e HMPV, podem tambÃm apresentar efeito anti-hemorrÃgico e prÃcoagulante, propriedades essas, importantes, visto que a complicaÃÃo de muitas viroses leva a quadros hemorrÃgicos. AlÃm disso, os PT de A. barbadensis nÃo apresentaram toxicidade expressiva, podendo ser utilizada como agente terapÃutico seguro e eficaz. / The aim of this study was to investigate the physicochemical and structural parameters of polysaccharides obtained from Aloe barbadensis leaves and to evaluate the antiviral and cytotoxic activities and procoagulant, anti-bleeding effects. In addition, toxicological analysis was carried out. The pulp was submitted to aqueous extraction (70 ÂC) and the total polysaccharides (PT) obtained by ethanol precipitation, TCA was used to remove the protein contamination. The fractionation of PT with DEAE-celulose resulted in two fractions (PI and PII). The physicochemical characterization showed that PI fraction presents mannose (78,4%), glucose (7,3%), galactose (2,1%), fucose (2,8%) and uronic acid (10,0%). Sulfate esters were not detected in PI fraction. On the other hand, PII fraction presents the monosaccharides mannose (39,2%), glucose (22,2%), galactose (26,3%), arabinose (3,8%), xylose (1,1%), uronic acids (8,0%) and sulfate esters groups (12,0%). The polysaccharidics of PII obtained by PAGE and agarose gel electrophoresis were revealed with toluidine blue and stainsall dye showing the presence of two different bands, one purple (indicative of sulfate) and another cyan (indicative of carboxilated groups). Structural analysis of PI and PII fractions by IR spectroscopy demonstrated that PI fraction is composed of residues of Ã-mannose O-acetylated (812.2 and 960 cm-1) and uronic acids (1738 cm-1). In contrast, the PII fraction is composed of mannose (1014.7 cm-1), galactose (1078.2 cm-1), negatively charged uronic acids (1635 cm-1) and sulfate ester (1329.5 and 1260.9 cm-1). These results corroborate with NMR analyses that suggest the presence of sulfate groups in PII structure. The cytotoxicity evaluation showed that PT and the fractions PI and PII did not show toxicity against most of tested cells and the same fractions were not effective against non-enveloped virus (Ad 19 and Ad 41) inhibition. However, the PT and PI fraction were able to inhibit the infection caused by HSV-1 and HSV-2. In addition, PII fraction presents antiviral activity against metapneumovirus. Although the PT and the fractions PI and PII did not show activity against dengue virus serotype 1 (DENV-1), PT could inhibit the bleeding effects in rats, reducing the bleeding and prothrombin time. The PT showed no toxicity in mice, but increased spleen size and number of blood platelets. In conclusion, A. barbadensis leaves contain neutral or negatively charged carboxylated/sulfated polysaccharides. In addition, besides having inhibitory activity against HSV-1, HSV-2 and HMPV, they can also anti-bleeding and procoagulant effect. Moreover, the PT of A. barbadensis showed no significant toxicity and can be used as a safe and effective therapeutic agent.