Human papillomavirus infection among sexual partners attending a Sexually Transmitted Disease Clinic in Rio de Janeiro, Brazil

Cervical cancer is a major source of illness and death among women worldwide and genital infection with oncogenic human papillomavirus (HPV) its principal cause. There is evidence of the influence of the male factor in the development of cervical neoplasia. Nevertheless, the pathogenic processes of HPV in men are still poorly understood. It has been observed that different HPV types can be found among couples. The objective of the present study was to investigate HPV infections in female patients (n = 60 females/group) as well as in their sexual partners and to identify the concordance of HPV genotypes among them. By using the polymerase chain reaction, we detected a 95% prevalence of HPV DNA in women with cervical intraepithelial neoplasia (CIN) compared to 18.3% in women with normal cervical epithelium, with a statistically significant difference (P < 0.001). The HPV DNA prevalence was 50% in male partners of women with CIN and 16.6% in partners of healthy women. In the control group (healthy women), only 9 couples were simultaneously infected with HPV, and only 22.2% of them had the same virus type, showing a weak agreement rate (kappa index = 0.2). Finally, we observed that HPV DNA was present in both partners in 30 couples if the women had CIN, and among them, 53.3% shared the same HPV type, showing moderate agreement, with a kappa index of 0.5. This finding supports the idea of circulation and recirculation of HPV among couples, perpetuating HPV in the sexually active population, rather than true recurrences of latent infections.

Permissivity of human HeLa cells to bovine adenovirus type 2 (BaV2 infection

Infection of hUlnan cells by bovine adenovirlls type 2 (BAV2) is abortive. To obtain a better understanding of this pllenomel1011, and in particular to identify Wllich steps in the viral replicative cycles are altered dllring this virlls-host cells interaction, we have llndertaken a detailed study of BAV2 infections of the nonpennissive hUlnan IIeLa cells. Using autoradiography and 3H-thymidine-labeled vvhole virus particles for infection of HeLa cells, vve determined that viral attachluent appears normal. Furthermore, Southern analysis revealed that internalization and transport to the nuclells occurs in BAV2 infected HeLa cells. To investigate viral DNi\ synthesis, infectivity assays involving hydroxyllrea, a viral DN-A synthesis inhibitor, were carried out. The results revealed that Bft:LV2 DNA synthesis does not occur in HeLa cells. Fllrtller investigations into viral early gene expression by northern blotting analyses indicated that HeLa cells fail to support expression of EIA. This suggested that abortive infection by BAV2 could be attributed to faiiure of EIA to express. To test the possibility that the failure to express ElA was due to the inability of the host cell to recognize the E lA prOlTIoter, ,ve carried out transient expression transfection experiments using plaslnids \vith the bacterial lacZ linder the control of either BAV2 or i\d5 EIA promoter. X-gal histochelIlical assays sho\ved expression of lacZ from the Ad5 ElA prOlnoter but no expression of lacZ [rOln the BAV2 EIA prOlTIoter. This further suggests that the abortive infection b:y BAV2 could be attributed to failure of EIA to express dlle to a nonfllnctional prOlTIoter in hlunan cells. Thus we speClllated that abortive infection of HeLa cells by adenoviruses may be averted by providing EtA functions in trans. To demonstrate this, we coinfected HeLa cells with Ad5 and BAV2, reasoning that Ad5 could cOlnpensate for EIA deficiency in BAV2. OUf results showed that BAV2 DNA synthesis was indeed Sllpported in HeLa cells coinfected with Ad5dlE3 as revealed by Southern analysis. In contrast, coinfection of HeLa cells \vith BAV2 and Ad5dlElE3 mutallt did not support BLt\V2 DNA synthesis. Interestingly, BAV2 failed to replicate in 293 cells which are constitlltively expressing the El genes. This could ilnply that El is necessary but not sufficient to avert the failllre ofBAV2 to undergo productive infection ofhulnan cells.

Dynamic epigenetic changes in immune responses to infection in human dendritic cells

La méthylation de l'ADN est une marque épigénétique importante chez les mammifères. Malgré le fait que la méthylation de la cytosine en 5' (5mC) soit reconnue comme une modification épigénétique stable, il devient de plus en plus reconnu qu'elle soit un processus plus dynamique impliquant des voies de méthylation et de déméthylation actives. La dynamique de la méthylation de l'ADN est désormais bien caractérisée dans le développement et dans le fonctionnement cellulaire des mammifères. Très peu est cependant connu concernant les implications régulatrices dans les réponses immunitaires. Pour se faire, nous avons effectué des analyses du niveau de transcription des gènes ainsi que du profilage épigénétique de cellules dendritiques (DCs) humaines. Ceux-ci ont été faits avant et après infection par le pathogène Mycobacterium tuberculosis (MTB). Nos résultats fournissent le premier portrait génomique du remodelage épigénétique survenant dans les DCs en réponse à une infection bactérienne. Nous avons constaté que les changements dans la méthylation de l'ADN sont omniprésents, identifiant 3,926 régions différentiellement méthylées lors des infections par MTB (MTB-RDMs). Les MTB-RDMs montrent un chevauchement frappant avec les régions génomiques marquées par les histones associées avec des régions amplificatrices. De plus, nos analyses ont révélées que les MTB-RDMs sont activement liées par des facteurs de transcription associés à l'immunité avant même d'être infecté par MTB, suggérant ces domaines comme étant des éléments d'activation dans un état de dormance. Nos données suggèrent que les changements actifs dans la méthylation jouent un rôle essentiel pour contrôler la réponse cellulaire des DCs à l'infection bactérienne.

Sexual sensation-seeking and worry about sexually transmitted diseases (STD) and human immunodeficiency virus (HIV) infection among Spanish adolescents. = B??squeda de sensaciones y preocupaci??n por las Enfermedades de Transmisi??n Sexual y VIH en adolescentes espa??oles

Resumen tomado de la publicaci??n. Resumen tambi??n en ingl??s

Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors

Background: Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (-31.1%), or were of mestizo (-24.6%) or black (-40.9%) ethnicity. Conclusions: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.

Infection of human airway epithelium by human and avian strains of influenza a virus

We describe the characterization of influenza A virus infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (HAE). Sialic acid receptors for both human and avian viruses, alpha-2,6- and alpha-2,3-linked sialic acids, respectively, were detected on the HAE cell surface, and their distribution accurately reflected that in human tracheobronchial tissue. Nonciliated cells present a higher proportion of alpha-2,6-linked sialic acid, while ciliated cells possess both sialic acid linkages. Although we found that human influenza viruses infected both ciliated and nonciliated cell types in the first round of infection, recent human H3N2 viruses infected a higher proportion of nonciliated cells in HAE than a 1968 pandemic-era human virus, which infected proportionally more ciliated cells. In contrast, avian influenza viruses exclusively infected ciliated cells. Although a broad-range neuraminidase abolished infection of HAE by human parainfluenza virus type 3, this treatment did not significantly affect infection by influenza viruses. All human viruses replicated efficiently in HAE, leading to accumulation of nascent virus released from the apical surface between 6 and 24 h postinfection with a low multiplicity of infection. Avian influenza A viruses also infected HAE, but spread was limited compared to that of human viruses. The nonciliated cell tropism of recent human H3N2 viruses reflects a preference for the sialic acid linkages displayed on these cell types and suggests a drift in the receptor binding phenotype of the H3 hemagglutinin protein as it evolves in humans away from its avian virus precursor.

Sole infection by human metapneumovirus among children with radiographically diagnosed community-acquired pneumonia in a tropical region

Background Limited information is available on the role of human metapneumovirus (HMPV) as the unique pathogen among children hospitalized for community-acquired pneumonia (CAP) in a tropical region. Objective We aimed to describe HMPV infection among children with CAP investigating bacterial and viral co-infections. Patients and methods A prospective study was carried out in Salvador, North-East Brazil. Overall, 268 children aged <5 years hospitalized for CAP were enrolled. Human metapneumovirus RNA was detected in nasopharyngeal aspirates (NPA) by reverse transcription polymerase chain reaction. Sixteen other bacterial and viral pathogens were investigated by an expanded panel of laboratory methods. Chest X-ray taken on admission was read by an independent paediatric radiologist unaware of clinical information or the established aetiology. Results Human metapneumovirus RNA was detected in NPAs of 11 (4.1%) children, of which 4 (36%) had sole HMPV infection. The disease was significantly shorter among patients with sole HMPV infection in comparison with patients with mixed infection (4 +/- 1 versus 7 +/- 2 days, P = 0.03). Three of those four patients had alveolar infiltrates. Conclusion Sole HMPV infection was detected in children with CAP in Salvador, North-East Brazil. HMPV may play a role in the childhood CAP burden.

Performance of the Quantitative Food Frequency Questionnaire Used in the Brazilian Center of the Prospective Study Natural History of Human Papillomavirus Infection in Men: The HIM Study

The Natural History of Human Papillomavirus (HPV) Infection in Men: The HIM Study is a prospective multi-center cohort study that, among other factors, analyzes participants` diet. A parallel cross-sectional study was designed to evaluate the validity and reproducibility of the quantitative food frequency questionnaire (QFFQ) used in the Brazilian center from the HIM Study. For this, a convenience subsample of 98 men aged 18 to 70 years from the HIM Study in Brazil answered three 54-item QFFQ and three 24-hour recall interviews, with 6-month intervals between them (data collection January to September 2007). A Bland-Altman analysis indicated that the difference between instruments was dependent on the magnitude of the intake for energy and most nutrients included in the validity analysis, with the exception of carbohydrates, fiber, polyunsaturated fat, vitamin C, and vitamin E. The correlation between the QFFQ and the 24-hour recall for the deattenuated and energy-adjusted data ranged from 0.05 (total fat) to 0.57 (calcium). For the energy and nutrients consumption included in the validity analysis, 33.5% of participants on average were correctly classified into quartiles, and the average value of 0.26 for weighted kappa shows a reasonable agreement. The intraclass correlation coefficients for all nutrients were greater than 0.40 in the reproducibility analysis. The QFFQ demonstrated good reproducibility and acceptable validity. The results support the use of this instrument in the HIM Study. J Am Diet Assoc. 2011;111:1045-1051.

Seroprevalence of Human Herpesvirus 8 Infection in Individuals From Health Care Centers in Mozambique: Potential for Endemic and Epidemic Kaposi`s Sarcoma

Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its prevalence in Mozambique is unknown. The seroprevalence of HHV-8 in a cohort of individuals seen at public health centers in Northern (n = 208), Central (n = 226), or Southern (n = 318) Mozambique was examined. All individuals were interviewed to obtain socioeconomic, demographic and clinical data and were tested for serum anti-HHV-8 antibodies using an immunofluorescence assay. The overall frequency of HHV-8 antibodies was 21.4% and, in spite of the diversity of epidemiological characteristics of the tested individuals, did not differ significantly among regions: 18.7%, 24.3% and 21.4% in the North, Center, and South, respectively (chi(2), 2.37; P = 0.305). The variables that were associated significantly with the presence of HHV-8 antibodies were gender, age, level of education, number of siblings and HIV serostatus, but these differed across the regions. In the North, although tested individuals lived under poor socioeconomic conditions, no association between HHV-8 infection and household variables was detected, with the exception of the number of siblings (P = 0.042). In the Central region, HHV-8 infection was associated with gender (P = 0.010), the number of household members (P = 0.031), and the place of attendance (P = 0.021). In the South, HHV-8 infection was associated with the number of siblings (P = 0.023) and HIV status (P = 0.002). The overall prevalence of HHV-8 seropositivity increased with age. These results demonstrate that Mozambique is another country in Africa with endemic HHV-8 infection, and, because of the AIDS epidemic, continued access to antiretroviral treatment is necessary to avert an outbreak of AIDS-Kaposi`s sarcoma. J. Med. Virol. 82:1216-1223, 2010. (C) 2010 Wiley-Liss, Inc.

Association of Human T Lymphotropic Virus 1 Amplification of Periodontitis Severity with Altered Cytokine Expression in Response to a Standard Periodontopathogen Infection

Background. Periodontal diseases (PDs) are infectious diseases in which periodontopathogens trigger chronic inflammatory and immune responses that lead to tissue destruction. Recently, viruses have been implicated in the pathogenesis of PDs. Individuals infected with human T lymphotropic virus 1 (HTLV-1) present with abnormal oral health and a marked increased prevalence of periodontal disease. Methods. In this study, we investigated the patterns of periodontopathogen infection and local inflammatory immune markers in HTLV-1-seropositive individuals with chronic periodontitis (CP/HTLV-1 group) compared with HTLV-1 -seronegative individuals with chronic periodontitis (CP group) and periodontally healthy, HTLV-1 -seronegative individuals (control group). Results. Patients in the CP/HTLV-1 group had significantly higher values of bleeding on probing, mean probing depth, and attachment loss than patients in the CP group. The expression of tumor necrosis factor a and interleukin (IL) 4 was found to be similar in the CP and CP/HTLV-1 groups, whereas IL-12 and IL-17 levels trended toward a higher expression in the CP/HTLV-1 group. A significant increase was seen in the levels of IL-1 beta and interferon gamma in the CP/HTLV-1 group compared with the CP group, whereas expression of the regulatory T cell marker FOXp3 and IL-10 was significantly decreased in the lesions from the CP/HTLV-1 group. Interestingly, similar frequency and/or load of periodontopathogens (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans) and frequency of viruses (herpes simplex virus 1, human cytomegalovirus, and Epstein-Barr virus) characteristically associated with PDs were found in the CP/HTLV and CP groups. Conclusions. HTLV-1 may play a critical role in the pathogenesis of periodontal disease through the deregulation of the local cytokine network, resulting in an exacerbated response against a standard periodontopathogen infection.

Putative outer membrane proteins of Leptospira interrogans stimulate human umbilical vein endothelial cells (HUVECS) and express during infection

Cell adhesion molecules (CAMs) are surface receptors present in eukaryotic cells that mediate cell-cell or cell-extracellular matrix interactions. Vascular endothelium stimulation in vitro that lead to the upregulation of CAMs was reported for the pathogenic spirochaetes, including rLIC10365 of Leptospira interrogans. In this study, we report the cloning of LIC10507, LIC10508, LIC10509 genes of L interrogans using Escherichia coli as a host system. The rational for selecting these sequences is due to their location in L. interrogans serovar Copenhageni genome that has a potential involvement in pathogenesis. The genes encode for predicted lipoproteins with no assigned functions. The purified recombinant proteins were capable to promote the upregulation of intercellular adhesion molecule 1 (ICAM-1) and E-selectin on monolayers of human umbilical vein endothelial cells (HUVECS). In addition, the coding sequences are expressed in the renal tubules of animal during bacterial experimental infection. The proteins are probably located at the outer membrane of the bacteria since they are detected in detergent-phase of L interrogans Triton X-114 extract. Altogether our data suggest a possible involvement of these proteins during bacterial infection and provide new insights into the role of this region in the pathogenesis of Leptospira. (C) 2008 Elsevier Ltd. All rights reserved.

Factors associated with increased prevalence of human papillomavirus infection in a cohort of HIV-Infected Brazilian women

Objectives: Human papillomavirus (HPV) infection is a major risk factor for cervical disease. Using baseline data from the HIV-infected cohort of Evandro Chagas Clinical Research Institute at Fiocruz, Rio de Janeiro, Brazil, factors associated with an increased prevalence of HPV were assessed. Methods: Samples from 634 HIV-infected women were tested for the presence of HPV infection using hybrid capture 11 and polymerase chain reaction. Prevalence ratios (PR) were estimated using Poisson regression analysis with robust variance. Results: The overall prevalence of HPV infection was 48%, of which 94% were infected with a high-risk HPV. In multivariate analysis, factors independently associated with infection with high-risk HPV type were: younger age (<30 years of age; PR 1.5, 95% confidence interval (CI) 1.1-2.1), current or prior drug use (PR 1.3, 95% CI 1.0-1.6), self-reported history of HPV infection (PR 1.2, 95% CI 0.96-1.6), condom use in the last sexual intercourse (PR 1.3, 95% CI 1.1-1.7), and nadir CD4+ T-cell count <100 cells/mm(3) (PR 1.6, 95% CI 1.2-2.1). Conclusions: The estimated prevalence of high-risk HPV-infection among HIV-infected women from Rio de Janeiro, Brazil, was high. Close monitoring of HPV-related effects is warranted in all HIV-infected women, in particular those of younger age and advanced immunosuppression. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is a worldwide health problem that may evolve to cirrhosis and hepatocellular carcinoma. Incompletely understood immune system mechanisms have been associated with impaired viral clearance. The nonclassical class I human leukocyte antigen G (HLA-G) molecule may downregulate immune system cell functions exhibiting well-recognized tolerogenic properties. HCV genotype was analyzed in chronic HCV-infected patients. Because HLA-G expression may be induced by certain viruses, we evaluated the presence of HLA-G in the liver microenvironment obtained from 89 biopsies of patients harboring chronic HCV infection and stratified according to clinical and histopathological features. Overall, data indicated that HCV genotype 1 was predominant, especially subgenotype 1a, with a prevalence of 87%. HLA-G expression was observed in 45(51%) liver specimens, and it was more frequent in milder stages of chronic hepatitis (67.4%) than in moderate (27.8%; p = 0.009) and severe (36.0%; p = 0.021) stages of the disease. Altogether, these results suggest that the expression of HLA-G in the context of HCV is a complex process modulated by many factors, which may contribute to an immunologic environment favoring viral persistence. However, because the milder forms predominantly expressed HLA-G, a protective role of this molecule may not be excluded. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier B.V. All rights reserved.