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The increased risk for opportunistic infections after a renal transplant requires monitoring of viral infections to avoid future complications. Our goal was to investigate the impact and factors associated with Epstein-Barr virus (EBV), human cytomegalovirus (HCMV) and human herpesvirus type 6 (HHV-6) viremia in renal transplant recipients. Whole blood samples were collected monthly from 82 patients during the first semester and then quarterly up to 1 year after transplantation. EBV, HCMV, and HHV-6 were detected and quantified by TaqMan real-time polymerase chain reaction. The results showed that EBV and HCMV viremia were detected in 32 patients (39% each), while HHV-6 viremia in only 3 patients (3.7%). EBV was significantly associated with age (P = .050), thymoglobuline induction (P = .019), mTOR inhibitor-based therapy (P = .003), and female gender (P = .044). HCMV was significantly associated with basiliximab induction (P = .015), mycophenolate mofetil (MMF)-based therapy (P = .003) and allograft acute rejection (P = .033). Moreover, HCMV-disease was correlated with MMF-based therapy (P = .021) and female gender (P = .003). In conclusion, EBV and HCMV viremia were associated with different immunosuppressive induction and maintenance strategies. Additionally, higher HCMV viremia (> 10 4 copies/mL) was related to acute allograft rejection.

Introduction: The genital infection by the human papillomavirus (HPV) can result in a sexually transmitted disease associated with precursor lesions for carcinogenesis in the genital tract. In recent years, evidence was accumulated defining HPV as the etiologic agent of cervical cancer; however, the etiology of penile cancer is still open and lacks studies. This study aims to contribute to the epidemiologic knowledge regarding the prevalence of this virus in malignant lesions of the male genital tract, using the DNA microarray assay, a technique that allows the simultaneous detection of up to 32 different HPV genotypes. Objective: The aim of this study was to investigate the presence of HPV in penile malignant lesions, to genotype HPV, when present, to correlate the HPV infection and its genotypes with the histopathological data. Methods: A total of 112 penile cancer samples was collected in a cross-sectional study. The detection methodology consisted of (1) detecting the presence of HPV DNA by the polymerase chain reaction (PCR) technique with generic primers, (2) genotyping the HPV using the DNA microarray assay, and (3) correlation of the histopathology, tumor invasiveness, and the dispersion of malignant cells by the lymph nodes with the presence of HPV. Results: The HPV prevalence was 57.1% (64). The most prevalent genotype was the HPV16 (32.8%), followed by HPV6 (23.4%); HPV18, HPV35, and HPV45 (12.5%); HPV31 (10.9%); and HPV70 (7.8%). Of the HPV-positive samples, 25% were mixed infections. Conclusion: The role of the HPV infection was significant within the multifactorial etiology of penile cancer. There was statistical significance between the lesion invasiveness and the presence of high-risk HPV infection. Thus, genotype surveillance can promote a better understanding of the role of HPV genotypes in male cancer development, and the DNA microarray assay proved to be an efficient tool for both the epidemiological study and the diagnostics of the HPV.

Our understanding of the phylogenetic and structural characteristics of the Merkel Cell Polyomavirus (MCPyV) is increasing but still scarce, especially in samples originating from South America. In order to investigate the properties of MCPyV circulating in the continent in more detail, MCPyV Viral Protein 1 (VP1) sequences from five basal cell carcinoma (BCC) and four saliva samples from Brazilian individuals were evaluated from the phylogenetic and structural standpoint, along with all complete MCPyV VP1 sequences available at Genbank database so far. The VP1 phylogenetic analysis confirmed the previously reported pattern of geographic distribution of MCPyV genotypes and the complexity of the South-American clade. The nine Brazilian samples were equally distributed in the South-American (3 saliva samples); North American/European (2 BCC and 1 saliva sample); and in the African clades (3 BCC). The classification of mutations according to the functional regions of VP1 protein revealed a differentiated pattern for South-American sequences, with higher number of mutations on the neutralizing epitope loops and lower on the region of C-terminus, responsible for capsid formation, when compared to other continents. In conclusion, the phylogenetic analysis showed that the distribution of Brazilian VP1 sequences agrees with the ethnic composition of the country, indicating that VP1 can be successfully used for MCPyV phylogenetic studies. Finally, the structural analysis suggests that some mutations could have impact on the protein folding, membrane binding or antibody escape, and therefore they should be further studied.

Non-melanoma skin cancers (NMSC) share similar risk factors with other virus-related cancers, despite the lack of proved causal association between viral infection and NMSC development. We investigated the presence of Merkel cell polyomavirus (MCPyV), Epstein-Barr virus (EBV), and human papillomavirus (HPV) DNA in 83 NMSC fresh-frozen and 16 non-cancerous skin biopsies and evaluated viral infection according to demographical data, histopathological diagnosis, and ultraviolet exposure. Our results showed that 75% of NMSC biopsies were positive for at least one out of three viruses, whereas only 38% of non-cancerous skin biopsies were positive (p = 0.02). Notably, HPV detection was frequent in NMSC (43%) and nearly absent (one sample, 6.7%) in non-cancerous biopsies (p = 0.007). MCPyV was associated with sites of higher exposure to ultraviolet radiation (p = 0.010), while EBV was associated with a compromised immune system (p = 0.032). Our study showed that HPV was strongly associated with NMSC while EBV and MCPyV with other risk factors. Though further studies are required to elucidate the role of viral infection in NMSC development and management, this study supports the possible role of oncogenic viruses in skin cancers, especially HPV.

BKV and JCV belong to the Polyomaviridae family and are opportunistic agents associated with complications in immunocompromised individuals. Although a single screening assay for both viruses would be convenient, the diversity of BKV and JCV serotypes and genotypes is a methodological challenge. In this paper, we developed a PCR method able to detect and segregate BKV and JCV, despite these genetic discrepancies. A duplex semi-nested PCR (duplex snPCR) was designed to target a conserved region (639nt-1516nt) within the VP2 gene. In the first PCR, a primer set common to all BKV and JCV serotypes/ genotypes was used, followed by a semi-nested PCR with internal primers for BKV and JCV segregation. The limit of detection of the duplex snPCR was as low as 10 copies of BKV or JCV plasmids/μL. Specific products were observed when JCV and BKV plasmids were mixed in the same reaction. In field sample testing, the duplex snPCR detected and distinguished both viruses in different biological samples. Results were confirmed by Sanger's sequencing. The geographical complexity of BKV and JCV serotypes and genotypes imposes limits to a simple and universal method that could detect each virus. However, we describe here a sensitive and reliable PCR technique for BKV and JCV diagnosis that overcomes these limitations and could be universally applied.

About 40 years ago, the large and small tumor antigens (LT-Ag and sT-Ag) of the polyomavirus (PyVs) simian vacuolating virus 40 have been identified and characterized. To date, it is well known that all the discovered human PyVs (HPyVs) encode these 2 multifunctional and tumorigenic proteins, expressed at viral replication early stage. The 2 T-Ags are able to transform cells both in vitro and in vivo and seem to play a distinct role in the pathogenesis of some tumors in humans. In addition, they are involved in viral DNA replication, transcription, and virion assembly. This short review focuses on the structural and functional features of the HPyVs’ LT-Ag and sT-Ag, with special attention to their transforming properties.

Introduction The genital infection by the HPV is among the most frequent sexually transmitted diseases (STD) worldwide, and it may result in lesions that can lead to the carcinogenesis of the genital tract. However, other factors may be associated with the onset or progression of the tissue malignancy process, such as the MCPyV, which may present oncogenic profile in the epithelial tissue. This study aims to investigate the presence of MCPyV and HPV in malignant lesions of the male and female genital tract, in order to contribute to the elucidation of the role of these viruses in the cellular malignancy process and to the epidemiological knowledge regarding the prevalence of both viruses in neoplastic lesions. Methods This is a cross-sectional study evaluating the prevalence of HPV and MCPyV infection in samples of cervical carcinoma and penile cancer. To date, we have obtained 112 samples of penile carcinoma and 31 samples of cervical carcinoma. So, we aim to detect the presence of HPV DNA by the polymerase chain reaction (PCR) technique using the generic primers MY09/MY11; to genotype HPVs by specific PCR to the E6 gene; to detect and quantify DNA of the MCPyV by the Nested PCR technique and real-time PCR; to investigate the presence of truncation mutations in the major T antigen of MCPyV. Results Results are partial. To date, all the male samples were analysed. We verified the presence of HPV in 54 (48.2%) of these samples, in which the most prevalent type was the HPV16 (66%). The cervical carcinoma samples are still under analysis. Conclusion The collection of cervical neoplasia samples is still being performed. In 2015, our research group found a case of multiple infection by HPV, MCPyV and Epstein-Barr virus in a case of squamous cell carcinoma of the penis in Rio de Janeiro. This was the first report of the presence of MCPyV in this type of penile lesion. Thus, we look forward to find results that contribute to the presence of MCPyV in genital malignant lesions and to elucidate its role in the oncogenic pathway of malignant lesions.

Zika virus (ZIKV) is an emergent arbovirus that has attracted attention in the last year as a possible causative agent of congenital malformation; it shows a remarkably increased microcephaly risk during otherwise healthy pregnancies. We present here an analysis of all ZIKV sequences available in Genbank up to April 2016, studying the mutations in the whole polyprotein and their possible structural implications for the proteins E, NS1, NS3 and NS5. This study suggests that microcephaly is not a consequence of any particular amino acid substitution but, conceivably, is a feature of ZIKV itself. Moreover, the structural analysis of ZIKV proteins, together with the mutational landscape of ZIKV and a structure-sequence comparison with other flaviviruses, allows the suggestion of regions that could be exploited as anti-ZIKV targets, including some allosteric sites found in the NS3 and NS5 proteins of DENV.

Background Merkel cell polyomavirus (MCPyV), a newly described oncogenic virus, has been found in association with tumours other than Merkel cell carcinoma (MCC). As yet, little is known about the involvement or influence of MCPyV on the development of these tumours and its prevalence in various populations. Aim To assess the prevalence of MCPyV DNA in cases of nonmelanoma skin cancer (NMSC). Methods The prevalence of MCPyV DNA was assessed in 96 cases of NMSC in a Brazilian population comprising 76 subjects, and these results were correlated with epidemiological and demographical data. Results MCPyV DNA was detected in 23 of 69 (33.3%) basal cell carcinomas, in 2 of 11 (18%) squamous cell carcinomas, 2 of 4 Bowen disease case, 0 of 1 MCC and 4 of 11 other skin disorders. Conclusion Despite the frequent detection of MCPyV DNA in NMSC, its possible role in the development of NMSC still needs further investigation.

SUMMARY The aim of this study was to investigate the association of EBV and HPV with gingivitis and/or periodontitis according to the immunologic status. To this end, 74 oral biopsies from transplanted and non-transplanted individuals with the abovementioned oral manifestations were submitted to a screening by PCR for both viruses. According to the results, EBV was strongly associated with gingivitis and/or periodontitis in transplanted individuals (p = 0.011) but not HPV (p = 0.766). EBV-HPV co-detections did not enhance the presence of tissue injury as well. Although a causal relationship was not investigated in this study, the higher frequency of these two oncoviruses in lesion tissues must be investigated in follow-up studies, especially among immunocompromised individuals.

Simultaneous Porcine circovirus type 2 (PCV-2) and Torque teno sus virus (TTSuV) infections have been reported around the world, generally linked to severe infections. In the present study, 257 swine plasma samples from 31 swine herds located in Brazil, were PCR screened for PCV-2 and TTSuV-1/2 and correlated with clinical data. PCV-2 was detected in 25%, followed by 38.1% and 42.4% of TTSuV-1 and TTSuV-2, respectively. Co-infections of two or three viruses were found in 32.3% of samples. PCV-2 was more frequently detected in the growing (p=0.030) and finishing phases (p=0.0005) while TTSuV-2 in the nursery (p=0.009). Only TTSuV-1 was statistically associated to clinical disease (multiple signs), in combination or not with PCV-2 or TTSuV-2 (p=0.015). PCV-2/TTSuV co-infections were more frequently related to weight gain reduction in comparison to mono-infections (p=0.049) and no-infections (p=0.027), and also in animals with (p=0.011) or without (p=0.037) clinical signs, being the nursery the most affected phase (p=0.025). Our results uphold the pathogenic potential of TTSuV in naturally infected pigs and the clinical/economical impact of this agent, especially in co-infections. Studies addressing the physiopathological mechanisms of simultaneous infections are needed.

We report here in first hand a case of triple infection caused by oncogenic viruses: HPV16, EBV-2 and MCPyV, in a squamous cell carcinoma of penis with an unfavorable outcome. Although reports on multiple viral infections in tumors are increasing, we do not know whether they are simply co-detected in the tissue or playing a synergistic role in the tumorigenesis. Studies addressing a putative co-stimulatory effect among these agents are needed in order to improve our comprehension of cell transformation.