Journal of Medical Virology最新文献

Mpox, formerly known as monkeypox, has re-emerged as a significant global health concern, particularly during the widespread outbreak of 2022. As an orthopoxvirus related to the eradicated smallpox virus, mpox has been primarily managed with smallpox vaccines and treatments, including the antiviral agent Tecovirimat. This systematic review aims to evaluate the effectiveness and safety of Tecovirimat in treating mpox, focusing on its use during the 2022 outbreak, especially among high-risk populations, including men who have sex with men and people living with HIV. We conducted a comprehensive search across databases, such as Embase, PubMed, and Web of Science, up to August 30, 2024. The selection involved a two-stage review process utilizing the Nested Knowledge platform, which helped streamline the screening and data extraction. We included studies that focused on the clinical efficacy and safety of Tecovirimat in human patients with confirmed mpox infections. Our analysis mainly synthesized data narratively due to the heterogeneity of study designs and outcomes. Fifteen studies met the inclusion criteria, providing data on 1031 mpox cases. The preliminary analysis of the PALM 007 RCT indicated that tecovirimat did not significantly outperform placebo in lesion resolution for all patients. Lesions healed faster than expected, regardless of tecovirimat or placebo treatment. A lower mortality rate of 1.7% among those enrolled in the PALM 007 RCT was observed, compared to the general mpox mortality rate of 3.6% or higher in the DRC. Observational studies revealed that early administration of Tecovirimat, especially within the first week of symptom onset, significantly improves symptom resolution, reduces the severity of the disease, and decreases the likelihood of hospitalization and complications in observational studies. However, the impact on viral clearance was inconsistent, and some studies suggested limited efficacy in severely immunocompromised patients. Regarding safety, Tecovirimat was generally well-tolerated as indicated by the RCT; however, mild adverse effects such as fatigue, headache, and nausea were commonly reported among observational studies. Serious adverse events were rare but included elevated liver enzymes and psychiatric symptoms, particularly in patients with pre-existing conditions. Tecovirimat demonstrates some potential benefits in treating mpox, particularly when administered early. The PALM 007 RCT failed to meet the efficacy point. Tecovirimat is generally well-tolerated with a favorable safety profile, although monitoring is advisable for those with existing liver or renal conditions. Despite promising results, further large-scale randomized controlled trials are needed to fully ascertain the drug's effectiveness across diverse populations and to explore its impact on viral clearance and transmission dynamics.

Rubella is listed as a disease that needs to be eliminated worldwide by the World Health Organization. This study aimed to investigate rubella epidemiology and genetic characteristics based on data from 12 years of laboratory-based surveillance (2009–2020) in Tianjin and to provide baseline genotype data for monitoring future rubella control efforts. We collected RV-positive throat swab samples from confirmed rubella cases during 2009–2020 in Tianjin to isolate RV, amplify and sequence target gene fragments, construct phylogenetic trees, and analyze nucleotide homologies. Four rubella isolates were chosen for whole genome sequencing. The epidemiological data of rubella cases were collected to describe and analyze the epidemiological characteristics of the rubella outbreak. Most cases (87.6%) occurred between March and June, and the peak incidence was observed in May. The age of the reported rubella cases ranged from almost 1 month to 82 years, most were between 10 and 29 years old (83.3%). Almost half (48.3%) of the confirmed rubella cases were from just four districts (Beichen District, Binhai New Area, Hebei District, and Nankai District). A total of 211 rubella virus strains were obtained during 2009–2020, phylogenetic analyses identified four lineages, including 1E-L1, 1E-L2, 2B-L1, and 2B-L2c, with high homologies of nucleotide sequences compared with RV strains from other provinces of China. Recombination analysis indicated that strain RVi/Tianjin.CHN/37.19/1 a possible recombination strain by 7 analysis methods, with p-values of 4.993 × 10⁻²⁸–2.922 × 10⁻⁴. Our study provided comprehensive data on rubella epidemiology and the first information on rubella genotypes in Tianjin. Clear evidence of recombination was found, indicating that RV has the potential to continually mutate, so close monitoring of the genetic variations of wild-type rubella virus strains is necessary. Rubella viruses were highly conserved at the genomic level, the incidence of rubella in Tianjin, as well as in China, has sustains at a low level, which gives us the idea that the rubella control and elimination goal could be achieved in the near future if strengthened RV surveillance continues and vaccine immunization coverage maintaining at the high level.

The high prevalence of cytomegalovirus (CMV) after kidney transplantation, along with its significant morbidity, mortality, and financial burden, makes it a serious infectious complication. This retrospective observational study aimed to determine the incidence of CMV infection and recurrence in renal transplant recipients during the era of immunosuppression (IS), and to identify modifiable predictors of CMV infection. A total of 233 patients were screened for CMV disease incidence and predictors and were prospectively followed. The incidence of CMV disease was found to be 14.6% (95% CI, 11.7%−18%), with no recurrence observed. Multivariate analysis revealed that factors such as CMV serostatus and a positive B-cell crossmatch at transplantation were associated with an increased risk of CMV. Specifically, patients with a positive B-cell crossmatch had a threefold higher risk of developing CMV compared to those with a negative crossmatch (p = 0.025). This association is a novel finding and should be considered when assessing risks and complications in patients. There was a lower incidence of CMV infection among kidney transplant recipients within the first 2−5 years after transplantation. A positive B-cell crossmatch at the time of transplantation was strongly associated with an increased risk of developing CMV disease.

With a multitude of HCC mouse models available, choosing the one that most closely resembles human HCC can be challenging. This study addresses this gap by conducting a comprehensive transcriptomic similarity analysis of widely used HCC mouse models. In this study, RNA-seq was performed on a model induced by double knockout of P53 and Pten via CRISPR/Cas9 in HBV-transgenic mice. Additionally, RNA-seq data from 2345 various other models induced by different methods were collected from GEO databases. The gene expression profiles, immune microenvironments, and metabolic pathways of these models were compared with those of human HCC. The analysis revealed distinct transcriptomic features among the different models. The HBV + P53&Pten KO model demonstrated the highest overall similarity to human HCC across various parameters. It shared a high degree of overlap in differentially expression genes (DEGs) between tumor and non-tumor tissues with human HCC, exhibited a transcriptome profile and immune cell infiltration pattern closely resembling human HCC, and showed metabolic alterations similar to those in human HCC. Conversely the DEN + CCl4-induced model showed the lowest similarity to human HCC in transcriptome profiles and DEGs and exhibited a distinct immune microenvironment with high NK cell infiltration, with minimal metabolic differences between tumor and non-tumor tissues. This study highlights the importance of selecting appropriate HCC mouse models for research. The HBV + p53&Pten KO model emerged as the most promising due to its remarkable similarity to human HCC across various aspects.

Emerging evidence underscores the pivotal role of long noncoding RNAs (lncRNAs) as crucial regulators within the HIV life cycle. However, the precise functions and detailed mechanisms by which lncRNAs operate in HIV-1 highly exposed but persistently seronegative (HESN) individuals remain currently unknown. Through RNA sequencing analysis of the HESN individual and the matched control, we identified potential lncRNAs. Then, we conducted validation experiments at the population level, while cellular models of HIV-1 infection were constructed for functional experimental investigations in vitro. Subcellular localization of the identified lncRNA was determined, followed by an exploration of the specific regulatory mechanism underlying HIV resistance through some experiments, such as RNA pull-down, western blot and Hirt assays. LncRNA LINC02453 is highly expressed in HESN. Moreover, LINC02453 is identified as a novel lncRNA associated with heightened resistance to HIV-1. LINC02453 is predominantly localized in the nucleus and binds to SEC13, a component of the nuclear pore complex, leading to the inhibition of HIV-1 replication by regulating key processes such as late reverse transcription, nuclear import, and DNA integration. Our findings suggest that LINC02453 may serve as a prospective target for the development of innovative anti-HIV therapeutics.

Hepatitis C virus (HCV) is a pathogenic virus of global health concern. The phylodynamics of HCV genotypes/subtypes 1a, 1b, 2, and 3 are explored only for specific geographic regions. However, their genome based global origin and detailed spatiotemporal spread, have yet to be extensively studied. To study the global evolution of “epidemic” HCV genotypes/subtypes, we screened all available HCV complete genome sequences (n = 2744) from 27 countries worldwide for over four decades. We used representative sequences (n = 516) for phylodynamic and phylogeographic analyses, examining HCV worldwide origin, transmission, and spatiotemporal spread. We are the first to study the global phylogeography of genotype 2. The evolutionary rates for genotype/subtype 1a, 1b, 2, and 3 are 1.109 × 10^-3, 1.096 × 10^-3, 5.013 × 10^-3 and 1.483 × 10^-3 substitutions/site/year respectively. We deduced tMRCAs and origin location of respective HCV genotype/subtype as 1909.21 (United States), 1893.36 (Japan), 981.76 (France), and 1714.89 (India). We estimated their migration pattern with time to and from different continents. The origin location of genotype 2 was estimated to be France instead of previous postulated African origin. This can be related to slave trade, French colonization, and previous studies on specific geographic regions only. HCV genotypes/subtypes showed transmission and expansion due to factors like World War II, iatrogenic infections, “baby boomer” population, inefficient medical screening, intravenous drug use, decline due to antiviral therapy introduction. Our study provides novel and extensive information about the evolutionary history and spatiotemporal spread of the HCV genotypes responsible for most infections worldwide.