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Cells infected with herpes simplex virus show a rapid cessation of protein synthesis and a dramatic decline in the levels of mRNA; a process known as host shutoff. This effect is attributed to a viral tegument protein called the virion host shutoff protein, or vhs. The mechanism by which vhs induces mRNA degradation is not yet understood. It is not known whether vhs possesses RNase activities or if it acts in combination with other cellular factors. To gain a better understanding of the function of vhs, I examined RNA degradation in detail by analyzing the RNA decay products generated in the presence of vhs. 𝘐𝘯 𝘷𝘪𝘷𝘰 experiments, performed by infecting murine erythroid leukemia cells with HSV, revealed that beta-globin mRNA is rapidly degraded, in the presence of vhs, without being converted to detectable decay intermediates. The half-life of this mRNA was 15 and 60 minutes for HSV-2 and HSV-1, respectively. Using vhs translated in a rabbit reticulocyte lysate system, I found that vhs induced rapid decay at the 5' end of a capped RNA molecule. The decay event was endonucleolytic and occurred at preferred sites downstream of the cap, generating capped oligonucleotides. Unlike influenza RNA polymerase, the cleavage event did not occur at a fixed distance from the cap since capped oligos of differing size were generated from different RNA substrates. My data indicate that vhs induced cleavage exhibits a strong, but not absolute preference for RNAs possessing an m⁷G cap, which may account for vhs' specificity for m RNAs 𝘪𝘯 𝘷𝘪𝘷𝘰. / Thesis / Master of Science (MSc)

Thirty-one (11 males and 26 females) individuals with recurrent genital herpes were recruited from two cities, 15 (five males and 10 females) from Blacksburg, Virginia and 16 (six males and 10 females) from Pittsburgh, Pennsylvania, to participate in a four Assessment Period (Before treatment, After treatment, 12-week Followup, and 26-week Followup) study. They were randomly assigned to one of three conditions: Psychosocial Intervention groups, Social Support groups, or Waiting-List control groups. Each condition was comprised of two, five-member groups (i.e., one group for each city), with six-members in the Pittsburgh Waiting-List condition. Two individuals of this latter group failed to complete the study . Six, consecutive, weekly, 96-minute group treatment sessions were conducted for the first two conditions, Waiting-List controls were offered treatment after the 26-week Followup period. Psychosocial Intervention involved: HSV information, interpersonal conflict discussions , relaxation training , stress management instructions, and suggestive-imagery techniques. The Social Support groups shared feelings and experiences about the disease, and served as placebo controls . Significantly greater reductions in herpes episode frequency, severity, and duration were reported by the Psychosocial Intervention individuals after treatment, than by individuals in the other two conditions. Similar improvements, in Psychosocial Intervention individuals, were found for the emotional distress, social support, and cognitive measures. It was concluded that Psychosocial Intervention was effective in reducing the chronicity of recurrent HSV infections as well as facilitating adjustment to the disease . Results were discussed according to psychoneuroimmunologic theory. / Ph. D. / incomplete_metadata

In CBA/NJ mice, splenic natural killer (NK) cell activity varies with stages of estrous. Susceptibility of ICR mice to intravaginal inoculation of herpes simplex virus type 2 (HSV-2) decreases with age. Susceptibility of female ICR and CBA/NJ mice to HSV-2 inoculated intravaginally and intraperitoneally was examined during the estrous cycle. In cycling ICR mice, greatest susceptibility to intravaginal inoculation was observed during diestrous and the least during metestrous. CBA/NJ mice were most susceptible to intravaginal inoculation of HSV-2 during diestrous. ICR mice were ovariectomized to mimic diestrous and found to be highly susceptible to intravaginal inoculation at all virus doses. No difference in susceptibility among phases of the estrous cycle was seen following intraperitoneal inoculation.

As infecções causadas pelo Herpes simplex virus, tipo 1 e 2 (HSV-1 e HSV-2) são consideradas problema de saúde pública no mundo, com prevalência em dois terços da população mundial. A doença é caracterizada pelo aparecimento de vesículas que ocasionam dor e constrangimento ao portador, devido à aparência desagradável que apresentam. As infecções que levam a lesões orofaciais são geralmente ocasionadas pelo HSV-1, enquanto as genitais, pelo HSV-2. O tratamento de escolha baseia-se no uso de antivirais em géis ou pomadas, entretanto, recidivas são comuns e dependentes do estado imunológico do indivíduo, além de exposição a fatores hormonais ou ambientais. Os anestésicos locais diminuem a dor ocasionada pela lesão além de mostrarem ter propriedades antivirais. A forma semissólida facilita a aplicação e a sua transformação em uma película fina, após curto período de tempo, favorece a manutenção da formulação no local, com aspecto final mais discreto quando comparada às opções disponíveis. O objetivo desse trabalho foi desenvolver e avaliar in vitro e in vivo formulações contendo anestésicos para o tratamento do herpes labial. Para tanto, duas formulações semissólidas formadoras de filme foram desenvolvidas e avaliadas (F1 e F1T), contendo HPMC K100, lidocaína (LIDO) e prilocaína (PRILO) combinados a adjuvantes, na presença (F1T) ou não (F1) do promotor de absorção Transcutol®. A mistura de PRILO e LIDO acarretou na formação de uma mistura eutética (ME). Para quantificação dos fármacos a partir da formulação, um método analítico por CLAE (Cromatografia Líquida de Alta Eficiência) foi revalidado e atendeu aos parâmetros preconizados na literatura. A recuperação dos fármacos a partir da pele suína foi satisfatória. As formulações apresentaram homogeneidade na distribuição do conteúdo. A formação do filme in situ foi avaliada e ocorreu em aproximadamente 20 minutos. A adição do promotor de absorção aumentou a concentração dos fármacos no líquido receptor no experimento de permeação passiva in vitro, utilizando pele de orelha suína. E a quantidade de PRILO e LIDO quantificada no estrato córneo foi maior para a formulação sem o Transcutol®. As análises reológicas de cisalhamento contínuo e oscilatório classificaram as formulações como fluídos newtonianos e a F1T apresentou maior estruturação em relação a F1. A avaliação in vitro da multiplicação viral sugere atividade virucida para ambos os fármacos, com proteção a infecção superior a 80% para as concentrações de fármaco avaliadas. As formulações não apresentaram irritação dérmica ao exame macroscópico. O teste in vivo de eficácia comprovou a capacidade dos anestésicos em regredir as lesões causadas por HSV-1. Sendo assim, as formulações propostas mostraram-se boas alternativas ao tratamento de lesões labiais causadas pelo HSV-1. Análises estatísticas adequadas foram realizadas. / Infections by Herpes Simplex virus, type 1 and 2 (HSV 1 e HSV-2) are a public health problem in the world with prevalence of two thirds of the mundial population. This disease is characterized by painful vesicles and embarrassment because of wound appearance. Orofacial wounds are mostly caused by HSV-1 and genital wounds are by HSV-2. Nowadays, current treatment is based on the use of antiviral in cream and ointments but, recurrences are very common and depend of individual state of immunological system besides environmental factors. Topical anesthetics minimize the pain and have shown antiviral properties. The semisolid composition improves application and its transformation into a thin film, after a short period of time, favors the maintenance at the site with good final aspect compared to the currently available treatment options. In this research, we developed and evaluated in vitro and in vivo compositions containing topical anesthetics for treatment of labials herpes. The compositions were prepared using HPMC K100, lidocaine (LIDO) and prilocaine (PRILO) combined with adjuvants, with permeation promoter Transcutol® (F1T) or not (F1). The mix of PRILO and LIDO results in eutectic mixture. For quantified drugs in compositions an analytical method by HPLC (High Performance Liquid Chromatography) was revalidated with satisfactory parameters, as well the recovery of drug on porcine skin. The formulations were with homogeneous content and film formation occurs in approximately 20 minutes. The addition of Transcutol® results in more PRILO and LIDO in receptor medium for F1T at in vitro passive permeation study. The quantify of drugs in corneum layer is mayor in F1 than F1T. Rheological analyses shown the compositions are newtonians fluids and F1T has more cohesion than F1. Evaluation of in vitro viral multiplication suggests activity before virus infects host cells, with 80% of protection of infection for evaluated concentrations. None composition shown dermal irritation in macroscopical examination. The in vivo efficacy study proves the anesthetics capacity of regress the HSV-1 wounds. Therefore, the developed compositions are good alternatives for labialis herpes caused by HSV-1.

A neuralgia pós-herpética é uma complicação da infecção pelo vírus da varicela zoster (VVZ). O nervo trigêmeo é acometido em cerca de 20-25% dos casos. Este estudo transversal teve como objetivo avaliar a sensibilidade orofacial de doentes com NPH trigeminal e identificar as características odontológicas da amostra. Foram utilizados os seguintes instrumentos de avaliação: exame sensitivo padronizado da face (algiometria, testes de sensibilidade térmica e táctil), questionário RDC/TMD, eixo I e II, (critérios de diagnóstico em pesquisa) para o diagnóstico de disfunção mandibular (DTM), protocolo para avaliação de dor orofacial (EDOF-HC), questionário McGill para avaliação de dor, exame periodontal (índice de placa - IP, índice de sangramento - IS, índice de profundidade clínica de sondagem - PCS e índice de profundidade clínica de inserção - PCI), e o índice CPO-D (somatória do número de dentes cariados, perdidos em razão de cárie dentária e restaurados). Houve diferença significativa entre o lado ipsolateral e o contralateral aos testes de sensibilidade no V1 com frio (p=0,038), vonFrey (p=0,008), alfinete (p=0,022) e algiometria (p=0,001); no V2 com frio (p=0,034), calor (p=0,019) e alfinete (p=0,037) e no V3 com frio (p= 0,042) e calor (p= 0,036); e na região intra-oral com alfinete (p=0,021). Dos 19 pacientes avaliados, 63,2% eram desdentados totais, a média do CPO-D foi de 28,3, a média do índice de placa foi de 48,0 e a média do índice de sangramento foi de 31,6. Neste estudo, 21% dos doentes relataram lesão na cavidade oral como sinal inicial do Herpes zoster. Com relação à condição músculo-esquelética da face (RDC/TMD), 78,9% tinha dor miofascial à palpação. Como conclusão destaca-se alteração de sensibilidade ipsolateral, mesmo nos ramos onde não houve erupção do VVZ, hipoalgesia em V1 e na mucosa oral ipsolateral; saúde oral comprometida, dor miofascial mastigatória e anormalidade da ATM na maioria dos doentes. / Postherpetic neuralgia is a complication after a varicella-zoster virus infection (VZV), affecting the trigeminal nerve in about 15-25% of the cases. This transversal study had the objective to evaluate the orofacial sensitivity and odontological characteristics of patients with trigeminal postherpetic neuralgia. The instruments used were: mechanical, thermal and pain sensory test, RDC/TMD questionnaire axis I and II (research diagnostic criteria for temporomandibular disorders), EDOF-HC protocol (for orofacial pain), McGill´s questionnaire, periodontal form (plaque index, blending index, clinical insertion and clinical deep level measures, to evaluate the periodontal disease as well the activity of disease) and DMFT index (Add of the number of teeth decayed, lost because caries and restored). There was significant difference compared the affected and the opposite side for tests of sensitivity at V1 with cold (p=0.038), vonFrey (p=0.008), pinpricks (p=0.022) and algiometric (p=0.001); at V2 with cold (p=0.034), heat (p=0.019) and pinpricks (p=0.037) and at V3 with cold (p = 0.042) and heat (p = 0.036) and in the intra-oral region with pinpricks (p=0.021). 63.2 % was edentulous, the average of the DMFT was 28.3, the average of the plaque\'s index was 48 and the average of the blending index was 31.6. In this study, 21 % of the patients reported lesion in the oral cavity like initial sign of the Herpes zoster. 78.9 % had myofascial pain with palpation (RDC/TMD). The main conclusions were alteration of sensitivity in the ipsolateral, even in the branches wherethere were no eruptions of the VVZ, hypoalgesia at V1 and oral mucosa ipsolateral; poor oral heath, masticatory myofascial pain and abnormality of the TMJ in the majority of the patients.

Background: Genital herpes is one of the most common sexually transmitted infections in the United States. As genital herpes is incurable and contagious, individuals with genital herpes face the decision to disclose their status to potential sexual partners with each new relationship formed. Such disclosure places individuals with genital herpes in a position to face rejection, which is commonly reported as one of the most concerning aspects of having genital herpes. The present study seeks to further understand the nature of genital herpes disclosure by addressing two core aims: 1) to understand determinants of and reasons for disclosure and non-disclosure and 2) to explore the relationship between past partner reactions to a disclosure and future intentions to disclose. Methods: Data on genital herpes disclosure experiences were collected via an online questionnaire, which was distributed through a variety of online channels including social media websites and email lists. Individuals who self-identified as having genital herpes and were 18 years and older were eligible for participation. Results: In examining Aim 1, the majority of participants (80.4%) disclosed to their last sexual partner. Age, relationship length, type of relationship, and expectations of a partner's response were significantly associated with the decision to disclose at the bivariate level. Expectations of a partner's reaction (AOR = .20, 95% CI .074-.539) and relationship type (AOR = 8.31, 95% CI 1.96-35.32) remained significant in multivariable modeling, explaining 45.2% of the variance in disclosure. Respondents who reported being in socially committed relationships and those who expected more positive partner reactions to a disclosure were more likely to disclose. Disclosure was also significantly associated with many romantic relationship building activities (e.g., establishing an exclusive relationship) but largely not associated with the sexual progression of a relationship. The decision to disclose was commonly multi-faceted, with the majority of participants reporting more than one reason that they did or did not disclose. Primary reasons for disclosure included "I wanted to be honest", "To protect my partner from getting herpes", and "It's my partner's right to know", while the most common reasons for non-disclosure were "I was concerned my partner would react badly", "I was ashamed", and "I was concerned that my partner would have rejected me". Regarding Aim 2, participants reported low levels of negative reactions and perceived rejection in response to their last disclosure experience. Intentions to disclose in the future were high among those who anticipated future sex partners. Discussion: The decision to disclose is often multi-faceted, and relationship characteristics play a key role in the decision to disclose. Among those who did disclose in this study, the majority did not report negative repercussions, including bad partner reactions and rejection. Future studies should examine if individuals are able to accurately assess potential partner reactions in order to better understand the differences between those who choose not to disclose and those who choose to disclose but experience a negative partner reaction or rejection.