In order to determine geographically related intratypic variation in human papillomavirus (HPV) type 16 and 18 isolates that could be associated with lesion development, data were analysed from an ongoing cohort study of the natural course of infection of HPVs and cervical neoplasia. Testing for HPVs was carried out by PCR and molecular variants of these HPVs were characterized by sequence analysis of the long control region and by dot blot hybridization of the E6 and L1 genes. Tests for HPV were done in multiple first-year specimens from 1690 women enrolled in a cancer screening program from 1993 to 1997. Subjects were followed-up by cytology and cervicography for detection of cervical lesions. Seven variants of HPV-16 and four of HPV-18 were detected in one or more specimens from 65 subjects. The same variant was found in specimens taken on different visits from each case of persistent infection. Overall, non-European variants tended to persist more frequently [odds ratio (OR)=4·5; 95% confidence interval (CI), 1·6–12·4] than European (E) variants (OR=2·5; 95% CI, 1·3–4·9), relative to the risk of persistence for non-oncogenic HPVs. In addition, non-E variants were more strongly associated with risk of both prevalent (age- and race-adjusted OR=172·2; 95% CI, 47·1–630·1) and incident [relative risk (RR)=22·5; 95% CI, 6·0–83·9] high-grade lesions than E variants (prevalent lesions OR=46·3; 95% CI, 15·5–138·0 and incident lesons RR=6·1; 95% CI, 1·3–27·4), relative to the risk for HPV-negative women. Although consistent, the latter differences were not statistically significant. If confirmed in other populations, measurement of intratypic variation of HPV-16 and -18 has the potential to serve as an ancillary tool in cervical cancer screening.

In Africa, Old World Primates are involved in the maintenance of sylvatic circulation of ZIKV. However, in Brazil, the hosts for the sylvatic cycle remain unknown. We hypothesized that free-living NHPs might play a role in urban/periurban ZIKV dynamics, thus we undertook an NHP ZIKV investigation in two cities in Brazil. We identified ZIKV-positive NHPs and sequences obtained were phylogenetically related to the American lineage of ZIKV. Additionally, we inoculated fourC.penicillatawith ZIKV and our results demonstrated that marmosets had a sustained viremia. The natural and experimental infection of NHPs with ZIKV, support the hypothesis that NHPs may be a vertebrate host in the maintainance of ZIKV transmission/circulation in urban tropical settings. Further studies are needed to understand the role they may play in maintaining the urban cycle of the ZIKV and how they may be a conduit in establishing an enzootic transmission cycle in tropical Latin America.

The pathogenesis of severe dengue disease involves immune components as biomarkers. The mechanism by which some dengue virus (DENV)–infected individuals progress to severe disease is poorly understood. Most studies on the pathogenesis of severe dengue disease focus on the process of antibody-dependent enhancement (ADE) as a primary risk factor. With the circulation of Zika virus (ZIKV) in DENV-endemic areas, many people infected by ZIKV were likely exposed to DENV. The influence of such exposure on Zika disease outcomes remains unknown. We investigated whether patients previously exposed to DENV exhibited higher viremia when exposed to a subsequent, heterologous dengue or Zika infection than those patients not previously exposed to dengue. We measured viral loads and cytokine profile during patients’ acute infections. Neither dengue nor Zika viremia was higher in patients with prior DENV infection, although the power to detect such a difference was only adequate in the ZIKV analysis. Of the 10 cytokines measured, only 1 significant difference was detected: Levels of interleukin 1β (IL-1β) were lower in dengue-infected patients who had experienced a previous dengue infection than patients infected with dengue for the first time. However, power to detect differences between groups was low. In Zika-infected patients, levels of IL-1β showed a significant, positive correlation with viral load. No signs of ADE were observed in vivo in patients with acute ZIKV infection who had prior exposure to DENV.

Open reading frame expressed sequences tags (ORESTES) differ from conventional ESTs by providing sequence data from the central protein coding portion of transcripts. We generated a total of 696,745 ORESTES sequences from 24 human tissues and used a subset of the data that correspond to a set of 15,095 full-length mRNAs as a means of assessing the efficiency of the strategy and its potential contribution to the definition of the human transcriptome. We estimate that ORESTES sampled over 80% of all highly and moderately expressed, and between 40% and 50% of rarely expressed, human genes. In our most thoroughly sequenced tissue, the breast, the 130,000 ORESTES generated are derived from transcripts from an estimated 70% of all genes expressed in that tissue, with an equally efficient representation of both highly and poorly expressed genes. In this respect, we find that the capacity of the ORESTES strategy both for gene discovery and shotgun transcript sequence generation significantly exceeds that of conventional ESTs. The distribution of ORESTES is such that many human transcripts are now represented by a scaffold of partial sequences distributed along the length of each gene product. The experimental joining of the scaffold components, by reverse transcription–PCR, represents a direct route to transcript finishing that may represent a useful alternative to full-length cDNA cloning.