Journal of Medical Virology最新文献

Macrophages are suspected to be involved in the pathogenesis of type 1 diabetes. The role of macrophages in the transmission of coxsackievirus B4 (CVB4) to pancreatic cells and in the alteration of these cells was investigated. Human monocytes isolated from peripheral blood were differentiated into macrophages with M-CSF (M-CSF macrophages) or GM-CSF (GM-CSF macrophages). M-CSF macrophages were inoculated with CVB4. M-CSF and GM-CSF macrophages were activated with lipopolysaccharide and interferon (IFN)-γ. Human pancreatic beta cells 1.1B4 were inoculated with CVB4 derived from M-CSF macrophages or were cocultured with CVB4-infected M-CSF macrophages. The antiviral activity of synthetic molecules in macrophage cultures was evaluated. Activated macrophages were cocultured with CVB4-persistently infected 1.1B4 cells, and the specific lysis of these cells was determined. Our study shows that CVB4 can infect M-CSF macrophages, leading to the release of interleukin-6 and tumor necrosis factor-α and later IFN-α. M-CSF macrophage-derived CVB4 can infect 1.1B4 cells, which were then altered; however, when these cells were cultured in medium containing agarose, cell layers were not altered. Fluoxetine and CUR-N373 can inhibit CVB4 replication in macrophage cultures. Supernatants of activated M-CSF and GM-CSF macrophage cultures induced lysis of CVB4-persistently infected 1.1B4 cells. The cytolytic activity of activated GM-CSF macrophages was higher towards CVB4-persistently infected 1.1B4 cells than mock-infected 1.1B4 cells. In conclusion, macrophages may play a role in CVB4 infection of pancreatic cells, and are capable of inducing lysis of infected pancreatic cells.

Cervical cancer screening is a cornerstone of cervical cancer elimination. Detection of high-risk human papillomavirus (hrHPV) is recommended as the first step in screening provided that the assay used has been adequately validated. The Sansure® Human Papillomavirus DNA Diagnostic Kit is a new assay designed to detect HPV16, HPV18 and 13 other HPV in aggregate. The study aimed to evaluate the intra- and interlaboratory reproducibility of the assay according to international guidelines. Five hundred and fifty cervical residual cell samples from women attending cervical cancer screening were selected from the biobank of the HPV National Reference Centre in Belgium and used in this study. After DNA extraction, HPV was tested using the Sansure® Human Papillomavirus DNA Diagnostic Kit. The lower 95% confidence limit around the general reproducibility of this assay should be greater than or equal to 87%, with κ ≥ 0.50. Five hundred and thirty-three samples had valid results. The Sansure® Human Papillomavirus DNA Diagnostic Kit demonstrated an excellent intra-laboratory reproducibility of 93.8% (95% confidence interval [CI]: 91.4–95.7, κ = 0.85). The interlaboratory reproducibility was 93.4 (95% CI: 91.0–95.4, κ = 0.84). Intra and interlaboratory reproducibility were also excellent at the genotype level. Excluding HPV53 single infection samples from the analyses also resulted in excellent agreement. These data show that the Sansure® Human Papillomavirus DNA Diagnostic Kit is highly reproducible.

Infertility, affecting approximately 16% of the global population, has led to increased reliance on reproductive medicine. The impact of human papillomavirus (HPV) infection in one or both partners on outcomes of Assisted Reproduction Technologies (ART) remains unclear. This prospective cohort study aimed to evaluate prevalence and effects of HPV infection in subjects and couples candidates to ART. A total of n = 510 men and n = 246 women were included and n = 145 couples (n = 290 individuals) had both partners enrolled in the study. The HPV semen infection rate was 17% (95% CI: 14–20) with HPV-42, HPV-16, HPV-53 and HPV-51 as the most frequently detected genotypes. In women, 26% (95% CI: 21–32) tested HPV-positive in cervical swabs. In 6% (95% CI: 3–11) of the couples, both partners were positive but only three couples shared the same genotypes (HPV-16; HPV-39, HPV-51, and HPV-42; HPV-31). Follicular fluids were positive in 20% (95% CI: 11–33) of samples, showing genotype discrepancies with cervical tests. Semen treatment could not completely eliminate the virus in positive samples but reduced the positivity to one-third. No significant differences in semen and embryological variables, clinical pregnancy and live birth rates, neonatal and obstetrics outcomes were observed in subjects with positivity in semen or cervix compared to respective negative groups. Cumulative live birth rates per oocyte retrieval in couples where both partners were negative or both were positive did not differ, being 37% (95% CI: 28%–47%) and 44% (95% CI: 19–73), respectively. In conclusion, HPV testing should not be considered a prerequisite for accessing ART treatments. Robust inferences for natural fertility cannot be made using our findings, as the ART setting does not fully reflect natural conditions.

Human papillomaviruses (HPVs) represent a diverse group of double-stranded DNA viruses associated with various types of cancers, notably cervical cancer. High-risk types of HPVs exhibit their oncogenic potential through the integration of their DNA into the host genome. This integration event contributes significantly to genomic instability and the progression of malignancy. However, traditional detection methods, such as immunohistochemistry or PCR-based assays, face inherent challenges, and thus alternative tools are being developed to fasten and simplify the analysis. Our study introduces an innovative biosensing platform that combines loop-mediated amplification with electrochemical (EC) analysis for the specific detection of HPV16 integration. By targeting key elements like the E7 mRNA, a central player in HPV integration, and the E2 viral gene transcript lost upon integration, we show clear distinction between episomal and integrated forms of HPV16. Our EC data confirmed higher E7 expression in HPV16-positive cell lines having integrated forms of viral genome, while E2 expression was diminished in cells with fully integrated genomes. Moreover, we revealed distinct expression patterns in cervical tissue of patients, correlating well with digital droplet PCR, qRT-PCR, or immunohistochemical staining. Our platform thus offers insights into HPV integration in clinical samples and facilitates further advancements in cervical cancer research and diagnostics.

Rotavirus A (RVA) is the main cause of acute gastroenteritis among children under the age of five globally. The unusual bat-like human RVA strains G3P[10] (RVA/Human-wt/THA/CMH079/05/2005/G3P[10] and RVA/Human-wt/THA/CMH-S015-19/2019/G3P[10]) were detected in children with acute gastroenteritis in 2005 and 2019, respectively, in the same geographical area of Northern Thailand. To elucidate the genetic backgrounds of these unusual or bat-like human RVA strains, the complete genome of these RVA strains was sequenced and phylogenetically analyzed. All eleven genome segments of these G3P[10] strains were genotyped as G3-P[10]-I8-R3-C3-M3-A9-N3-T3-E3-H6, which is closely related to bat G3P[10] RVA strain (RVA/Bat-tc/CHN/MYAS33/2013/G3P[10]) and bat-like human RVA strain (RVA/Human-wt/THA/MS2015-1-0001/2015/G3P[10]). The findings indicate that human G3P[10] RVA strains detected in this study (RVA/Human-wt/THA/CMH079/05/2005/G3P[10] and RVA/Human-wt/THA/CMH-S015-19/2019/G3P[10]) contained all eleven genome segments similar to those of bat RVA strains and appeared to be human RVA strains of bat origin. Phylogenetic analysis revealed that several genome segments of these two RVA strains were also closely related with those of other species in addition to bats and had a zoonotic transmission history. The results of this study supported the roles of interspecies transmission of RVA strains among bats and humans in the natural environment and provided convincing evidence that the evolution of human RVAs was closely interrelated with those of animal RVAs. Continuing surveillance of RVAs in humans and animals is imperative to gain a better understanding of the origin and the evolution of these viruses.

The Orthobunyavirus oropoucheense species encompasses a group of arthropod-borne zoonotic viruses transmitted by biting midges to animals including humans. Several large-scale human outbreaks caused by the prototype member of this species, Oropouche virus (OROV) have been documented since the 1970s and were primarily confined to the Amazon basin. However, since 2022, more widespread OROV outbreaks have been unfolding in Brazil and across South America, with cases exported to Cuba, Italy, Spain, USA and Germany. In Brazil, the virus has reached and established communitary transmission in all geographic areas of the country. We isolated, characterized the cytopathic effect and recovered the full genome of two OROV isolates from the 2022–24 outbreak detected in patients from the Pernambuco state. Phylogenetic data supports a direct introduction from the Amazonas state, the epicenter of the epidemics in the country. As case counts accumulate in the state mounting evidence is supporting the establishiment of sustained transmission chains. Continued studies are critical to understand the transmission cycle in this region, including the most important vectors and reservoirs, to appropriately deploy control measures.

Respiratory syncytial virus-associated acute respiratory infection (RSV-ARI) constitutes an emerging cause of morbidity in the adult population. The present retrospective study was aimed at identifying factors predictive of poor outcome that may be assessed at the first evaluation in the Emergency Department (ED). We included 275 adult patients with laboratory-confirmed RSV-ARI that required hospital admission from the ED between January 2018 and December 2019. Poor outcome (composite of progression to high-flow oxygen therapy, non-invasive or invasive mechanical ventilation, or intensive care unit admission, and/or 30-day all-cause mortality) occurred in 31 patients (11.2%). Immunosuppression was present in 59 patients (21.5%). Although bacterial co-infection was rare, antibiotic therapy was commonly initiated. Ribavirin was administered in 10 patients. Cognitive impairment (odds ratio [OR]: 2.452; 95% confidence interval [CI]: 0.990–6.072), concurrent oral anticoagulation (OR: 3.099; 95 CI: 1.287–7.464) and a pulse oximetry oxygen saturation to fraction of inspired oxygen ratio (SpO₂/FiO₂) ratio <382 at ED admission (OR: 3.013; 95 CI: 1.306–6.950) were independent risk factors for poor outcome, whereas influenza vaccination in the current season was protective (OR: 0.324; 95% CI: 0.138–0.763). Various factors easily available at the ED are useful for early risk stratification in adult patients with RSV-ARI.