<p>Uvod: Varičela (Varicella, Ovčije boginje) i herpes zoster (Herpes Zoster) su bolesti koje izaziva virus varicella - zoster. Varičela spada u najče&scaron;će dečje osipne groznice. Herpes zoster je bolest ljudi starijeg životnog doba. Imunizacija protiv varičele i herpes zostera je dala značajne rezultate u prevenciji ovih bolesti. Raspoloživi epidemiolo&scaron;ki pokazatelji nisu dovoljni za uvođenje adekvatnog programa imunizacije protiv ovih bolesti u na&scaron;oj zemlji. Cilj istraživanja bio je da se na teritoriji Vojvodine utvrde: seroprevalencija varicella-zoster virusnih antitela, epidemiolo&scaron;ke karakteristike obolelih od varičele u periodu 1994&minus;2014. godine i obolelih od herpes zostera u periodu 1997&minus;2005, uzrasno specifične incidencije i udeo hospitalizovanih u ukupnom broju obolelih od varičele odnosno herpes zostera u periodu 2010&minus;2014. godine. Materijal i metode: Istraživanje epidemiolo&scaron;kih karakteristika varičele i herpes zostera je sprovedeno retrospektivno, analizom podataka iz epidemiolo&scaron;kog nadzora. Seroepidemiolo&scaron;ko istraživanje je sprovedeno prospektivno (april 2015&minus;februar 2016). Prikupljeno je 3.570 rezidualnih seruma uz prethodno informisanje i pisanu saglasnost pacijenata. Uzorak je reprezentativan za populaciju Vojvodine, prema mestu stanovanja, polu i uzrastu. Imunokompromitovani i primaoci transfuzije krvi u poslednjih &scaron;est meseci su izuzeti iz istraživanja. Testiranje seruma je sprovedeno ELISA testom u Centru za virusologiju Instituta za javno zdravlje Vojvodine. Referentna evropska laboratorija prosledila je referentni panel seruma koji je testiran pre i tokom testiranja banke seruma. Standardizacija rezultata je sprovedena na osnovu jednačine koju je prosledio Public Health England (PHE). Izračunata je i analizirana seroprevalencija antitela u odnosu na uzrast, pol i područje stanovanja. Istraživanje incidencije hospitalizovanih slučajeva varičele i herpes zostera sprovedeno je retrospektivno prikupljanjem podataka o hospitalizacijama. Statistički značajnim smatrane su vrednosti na nivou značajnosti p &lt; 0,05 a visoko statički značajnim p &lt; 0,01. Rezultati: Seroprevalencija antitela protiv virusa varicella-zoster u testiranom uzorku populacije Vojvodine je 84%. Utvrđen je očekivano visok procenat seropozitivne dece do navr&scaron;enih devet godina života (73,3%). Osim u uzrasnim grupama &lt; 1 i 1&minus;4 godine, seroprevalencija raste sa uzrastom. Varičela se u Vojvodini održava endemo-epidemijski sa visokim incidencijama. U posmatranom periodu, najvi&scaron;a uzrasno specifična incidencija varičele se registruje u uzrastu 5&minus;9 godina (5.824,6/100.000 stanovnika) i 0&minus;4 godine (5.000,7/ 100.000 stanovnika). Od varičele su če&scaron;će obolevali mu&scaron;karaci dok su žene značajno će&scaron;će obolevale od herpes zostera (p = 0,000 &lt; 0,01). Incidencije varičele i herpes zostera se značajno razlikuju u odnosu na mesto stanovanja. Udeo hospitalizovanih u ukupnom broju obolelih od varičele bio je od 0,7 do 0,9%. Najvi&scaron;a uzrasno specifična incidencija hospitalizovanih sa varičelom registrovana je u uzrastu 0&minus;4 godine i opada sa uzrastom. Incidencija herpes zostera najvi&scaron;a je kod starijih od 60 godina života (970,2/100,000 stanovnika), dok je incidencija hospitalizovanih slučajeva herpes zostera najvi&scaron;a kod starijih od 65 godina (105,7/100.000). Udeo hospitalizovanih slučajeva herpes zostera u ukupnom broju obolelih od herpes zostera se kretao u rasponu od 2,2 do 3,6 % ( &ge;2% ). Zaključak: Rezultati ovog istraživanja ukazuju da varičela i herpes zoster značajno opterećuju zdravstveno stanje na&scaron;eg stanovni&scaron;tva zbog čega postoji osnov za uspostavljanje epidemiolo&scaron;kog nadzora i kreiranje adekvatnog programa imunizacije.</p> / <p>Introduction: Varicella (Varicella, Chicken pox) and herpes zoster (Herpes Zoster) are diseases caused by the Varicella- zoster virus. Varicella is the most common children&#39;s rash-causing fever. Herpes zoster is mainly a disease of elderly people. Immunisation against varicella and herpes zoster have led to significant results in the prevention of these diseases. Available epidemiological indicators are not sufficient for introduction of an adequate program of immunization against these diseases in our country. The aim of the research was to establish: seroprevalence of varicella-zoster virus antibodies, the epidemiological characteristics of patients with varicella in the period 1994-2014. and patients with herpes zoster in the period 1997-2005, age-specific incidence and share of hospitalized patients in the total number of patients with varicella and herpes zoster in the period 2010-2014, in Autonomous Province of Vojvodina. Material and methods: The study of epidemiological characteristics of varicella and herpes zoster was conducted retrospectively by analyzing data from epidemiological surveillance. Seroepidemiological study was conducted prospectively (April 2015- February 2016). The total of 3.570 residual sera were collected with previously taken written informed consents of patients. Immunocompromised patients and recipients of blood transfusions in the last six months were not included in the survey. The sample was representative by residence, sex and age for population of Vojvodina. Testing of sera was conducted by ELISA tests at the Center for virusology, Institute of Public Health of Vojvodina. Reference European laboratory forwarded the reference panel serum which was tested before and during the testing of serum bank. Standardization of the results was based on the equation previously sent by Public Health England (PHE). Seroprevalence of antibodies was calculated in relation to the age, sex and area of residence. Incidence of hospitalized cases of varicella and herpes zoster was determined by retrospective collection of hospitalization data. Statistically significant was considered values at a significance level of p &lt; 0,05 and highly statistically significant at p &lt; 0,01. Results: The seroprevalence of antibodies against Varicella- zoster virus in the sample of the population of Vojvodina was 84%. High percentage of seropositive children under the age of nine years of age (73,3%) was determined, as expected. The seroprevalence increases with age, except in the age groups &lt;1 and 1-4. Varicella in Vojvodina maintains endemo-epidemic mode with high incidence. In the observed period, the highest age-specific incidence of varicella is registered in the age group 5-9 years (5.824,6/100.000 inhabitants) and at the age of 0-4 years (5.000,7/100.000 inhabitants). Varicella was found significantly more often in men while herpes zoster was more often in women (p= 0,000 &lt;0,01). Incidence of varicella and herpes zoster significantly varied among the population of certain municipalities in Vojvodina. The share of hospitalized patients in the total number of patients with varicella ranged from 0,7 to 0,9%. The highest age-specific incidence of hospitalized patients with varicella was registered in the age of 0-4 years and decreases with age. The incidence of herpes zoster is highest in people over 60 years of age (970,2/100.000 inhabitants), whereas the incidence of hospitalized cases of herpes zoster was highest in patients over 65 years (105,7/100.000). Proportion of hospitalized cases in the total number of patients with herpes zoster ranged from 2,2 to 3,6% . Conclusion: The results of this study suggest that varicella and herpes zoster are significant burden of the health status of our population and there is a basis for the establishment of epidemiological surveillance and creation of an adequate program of immunization.</p>

Herpes zoster is a common disease, affecting up to 30% of the population in their lifetime. We examined the burden of this disease over the period of 1997-2013 using administrative healthcare data to determine changes over time. Key medications used to treat herpes zoster and postherpetic neuralgia became generic, resulting in costs reductions, where was offset by increased drug utilization leaving drug-episode costs unchanged. Mean per-episode medical costs increased moderately. Combined, these resulted in increased outpatient costs over time. However, dramatic reduction in HZ-related hospitalizations countered these trends, resulting in no net change in overall burden. The total healthcare cost of treating HZ and PHN in Manitoba in 2011/12 was $1,997,183, slightly less than the $2,095,633 burden determined for 1997/98, the first study year. Long-term demographic projections suggest the population will continue to grow and age, likely driving the future burden upwards. / October 2016

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / The general problem of alteration in viral susceptibility by the irradiation of monolayers of tissue cells in culture was examined in this study; specifically an increased susceptibility of HeLa (an established cell line which was derived from an epidermaid carcinoma of the cervix) to destruction by herpes simplex virus (the virus commonly associated with cold sores or fever blisters). The experimental procedures included the study of the radiosensitivity of the cell line, survival curve analyses expressed as the efficiency of plating, that is the per cent of viable cells capable of forming colonies visible to the unaided eye within twelve days, and finally infectivity studies. Tissue culture has proved to be a very useful tool in the study of radiation effects on tissues of higher animals since the effects of radiation can apparently be explained on the cellular level. Many types of cells have been studied but in all cases the most striking characteristic in irradiated populations is the increased cell size. Ionizing radiation effects both the reproductive and synthesizing capacity of cells with the former being the more sensitive. Some irradiated cells never divide while others divide several times before reproduction stops. After the cells stop dividing, they continue to grow in size forming giants because synthesis of the cellular constituents continues. Giant cells resulting from x-irradiation are more readily destroyed by the action of viruses than are non-irradiated cells. PUCK & MARCUS reported that NDV when plated on a mixture of giant and normal cells, destroyed more of the giants than normal cells. An enhancement of cell susceptibility following irradiation was also demonstrated for two enteroviruses by HSIUNG. The increased susceptibility of x-ray-induced giant cells to CPE of virus and the earlier release of virus by such cells was also demonstrated by LEVINE in studies with the Leon strain of type 3 polio. Many tissue culture-virus systems have been used to demonstrate alterations in susceptibility induced by x-irradiation, but few investigators have used a HeLa-HSV system to study this altered susceptibility using low levels of irradiation (50 roentgens to 500 roentgens) [TRUNCATED] / 2031-01-01

Herpes simplex virus type 1 (HSV-1) is a virus commonly causing cold sores in humans, however, virulent infections are known to produce debilitating encephalitis and death. HSV-1 transcription is carried out by the host cell RNA polymerase II in a tightly regulated temporal cascade. The first genes transcribed, the a genes, are activated in the absence of viral DNA synthesis. Transcription of the other temporal classes, the β, βγ, and γ genes is dependent upon the protein products of the a genes for activation. The purpose of this study was to investigate the factors that contribute to this rigid regulation of HSV-1 transcription. This investigation sought to identify some of the cellular and viral transcription factors that activate transcription of genes of the later kinetic classes. Two separate approaches were utilized in these investigations. 1) In vitro transcription using a soluble, cell free system to study the transcriptional regulation of the VP5 gene, and 2) DNA competition binding assays to identify and characterize the protein-DNA complexes resulting from interaction between the cisacting DNA sequences of the VP5 gene, other viral genes, and the proteins that bind to them. Attempts at in vitro transcription of β, βγ, and γ genes were unsuccessful. Because these genes require a products for activation, it was necessary to prepare nuclear extracts from infected cells. However, HSV-1 contains endogenous RNase activities which are components of the biochemical machinery by which the virus directs host transcription to the synthesis of viral molecules. The uses of virus deficient in the host shut-off function and various drugs were unsuccessful. Previous work in the Millette laboratory demonstrated a sequence in the VP5 promoter that played a significant role in the up regulation of expression of that gene. DNA binding competition studies using a number of HSV-1 sequences exhibiting partial homology to this sequence demonstrated that these sequences all compete for the binding of the same protein factor. Similarly, a piece of the human immunodeficiency virus (HIV) exhibiting a seven base pair homology also exhibited weak competition.

This thesis defines a novel role for the Herpes Simplex Virus (HSV) tegument protein, virion protein (VP) 11/12 as a modulator of host cell signalling. Studies aimed at examining infection induced lymphocyte inactivation, revealed that VP11/12 is tyrosine phosphorylated in three lymphocyte lineages (T cell, B cell and NK cell) following exposure to HSV-1 or HSV-2 infected fibroblasts. Tyrosine phosphorylation of VP11/12 was greater in lymphocytes compared to fibroblasts or epithelial cells and phosphorylation was enhanced by the lymphocyte specific Src family kinase (SFK) Lck during transfection- or infection-based assays. This suggested that VP11/12 is a substrate of Lck or a kinase activated by Lck. Lck is best known for initiating intracellular signalling downstream of the T cell receptor (TCR) and NK cell receptors. However, VP11/12 null HSV mutants retained the ability to block TCR signalling and NK cell cytotoxicity. Phosphorylation of VP11/12 occurred in the absence of any known Lck stimulus, like TCR ligation. Infection alone may activate Lck since Lck in infected Jurkat cells displayed features characteristic of activation: a reduced electrophoretic mobility in sodium dodecyl sulphate polyacrylamide gel and a marked increase in phosphorylation at the activation loop tyrosine (Y394). SFK substrates sometimes activate their cognate kinase through high affinity binding of the SFK Src homology (SH) 2 or SH3 domains. VP11/12 may serve this dual function since it interacts with Lck or Lck signalling complexes and is strictly required for Lck activation during infection. SFKs including Lck lie upstream of the canonical phosphoinositide 3-kinase (PI3K)-Akt pathway in signalling emanating from immune receptors, growth factor receptors and polyoma middle T antigen (MTAg). In HSV infection of Jurkat T cells and human embryonic lung fibroblasts, we find that VP11/12 interacts with PI3K either directly or indirectly and is required for infection induced activation of the PI3K-Akt signalling pathway. SFK activity is required for tyrosine phosphorylation of VP11/12, VP11/12-PI3K interactions, and Akt activation in infected fibroblasts. This data suggests that VP11/12 orchestrates signalling analogous to that of MTAg. In this model, VP11/12 activates SFKs to induce its own phosphorylation, subsequently allowing for interactions with PI3K and activation of Akt. / Virology

HSV-2 may have adverse consequences in HIV. I evaluated the impact of HSV-2 co-infection on (highly active antiretroviral therapy)-untreated HIV infection in a systematic review of observational studies (study 1) and a retrospective cohort (study 2). I further evaluated whether HSV reactivation rates in co-infected persons differ by use of suppressive cART (study 3). Study 1 found modest evidence that HSV-2 seropositivity may be associated with accelerated progression to opportunistic infection or clinical AIDS, but not with increased HIV viral load. Some evidence suggests that HSV-2 disease activity is associated with increased HIV viral load and decreased CD4 counts. Study 2 compared rates of CD4 count change by HSV-2 status (Focus HerpeSelect ELISA) among 218 patients with a past period of ART-untreated follow-up using mixed linear regression models. No significant difference in the rate of CD4 count change was observed in HSV-2 seropositives at +13.6 cells/mm3/year (p=0.12) in univariate analysis, and -4.5 cells/mm3/year (p=0.68) in analysis adjusted for sex, HSV-1, oral and genital HSV symptoms, immigrant status, and immigrant*time interaction. These findings support the need for carefully designed and executed studies of HSV-2 suppression as an adjunctive management strategy for HIV disease, but raise questions regarding the exact mechanism of negative synergy between these viruses and the relative importance of HSV-2 latency and replication in driving these effects. In Study 3, 44 cART-naïve and 41 treated (HIV RNA<50 copies/mL) HIV+ adults with HSV-1 and/or 2 co-infection collected oral, genital and anal swabs daily for 28 days. Negative binomial models were used to quantify the relationship between cART and HSV shedding (Roche LightCycler HSV1/2). Overall HSV shedding was low, at a median (IQR) of 3.6% (0, 14.3%) of days. No relationship was seen between cART and HSV-1 or 2 shedding in univariate (RR=1.55, 95%CI=0.83,2.87) or multivariate analysis adjusted for sex, baseline CD4, recent immigrant status, and time since HIV diagnosis (aRR=1.05, 95%CI=0.43,2.58). Null results were also observed for HSV-1 and HSV-2 considered separately. That HSV shedding persists despite cART suggests that trials of anti-HSV drugs for improving HIV outcomes may be warranted in such patients.

Thesis (Ph. D.)--University of Chicago, Committee on Virology, 2001. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--University of Chicago, Committee on Virology, June 2001. / Includes bibliographical references. Also available on the Internet.

No description available.

HSV-2 may have adverse consequences in HIV. I evaluated the impact of HSV-2 co-infection on (highly active antiretroviral therapy)-untreated HIV infection in a systematic review of observational studies (study 1) and a retrospective cohort (study 2). I further evaluated whether HSV reactivation rates in co-infected persons differ by use of suppressive cART (study 3). Study 1 found modest evidence that HSV-2 seropositivity may be associated with accelerated progression to opportunistic infection or clinical AIDS, but not with increased HIV viral load. Some evidence suggests that HSV-2 disease activity is associated with increased HIV viral load and decreased CD4 counts. Study 2 compared rates of CD4 count change by HSV-2 status (Focus HerpeSelect ELISA) among 218 patients with a past period of ART-untreated follow-up using mixed linear regression models. No significant difference in the rate of CD4 count change was observed in HSV-2 seropositives at +13.6 cells/mm3/year (p=0.12) in univariate analysis, and -4.5 cells/mm3/year (p=0.68) in analysis adjusted for sex, HSV-1, oral and genital HSV symptoms, immigrant status, and immigrant*time interaction. These findings support the need for carefully designed and executed studies of HSV-2 suppression as an adjunctive management strategy for HIV disease, but raise questions regarding the exact mechanism of negative synergy between these viruses and the relative importance of HSV-2 latency and replication in driving these effects. In Study 3, 44 cART-naïve and 41 treated (HIV RNA<50 copies/mL) HIV+ adults with HSV-1 and/or 2 co-infection collected oral, genital and anal swabs daily for 28 days. Negative binomial models were used to quantify the relationship between cART and HSV shedding (Roche LightCycler HSV1/2). Overall HSV shedding was low, at a median (IQR) of 3.6% (0, 14.3%) of days. No relationship was seen between cART and HSV-1 or 2 shedding in univariate (RR=1.55, 95%CI=0.83,2.87) or multivariate analysis adjusted for sex, baseline CD4, recent immigrant status, and time since HIV diagnosis (aRR=1.05, 95%CI=0.43,2.58). Null results were also observed for HSV-1 and HSV-2 considered separately. That HSV shedding persists despite cART suggests that trials of anti-HSV drugs for improving HIV outcomes may be warranted in such patients.