Intervirology最新文献

Background: For foamy virus, the transactivator of spumaretrovirus (Tas) could bind directly to target DNA sequences termed as Tas responsive elements and trigger the viral internal promoter (IP) and long terminal repeat (LTR) promoters. The cellular endogenous factors also play an important role in viral gene expressions. We hypothesized that except the viral transcription factor Tas, the cellular endogenous factors also affect the viral gene expression.

Methods: The full length of the prototype foamy virus (PFV) genome (U21247) was used to predict the potential binding sites of the transcription factors by online software JASPAR (http://jaspar.genereg.net) and Softberry (http://linux1.softberry.com/berry.phtml?topic=index&group=programs&subgroup=promoter). The Dual-Luciferase® Reporter Assay System (Promega, USA) was used to confirm the relative luciferase activities of the test groups. The different representative activating agents or inhibitors of each canonical signal pathway were used to identify the impact of these pathways on PFV 5'LTR and IP promoters.

Results: The results showed different cellular endogenous factors might have respective effects on PFV 5'LTR and IP. It is worth mentioning that activator protein-1 and BCL2-associated athanogene 3, 2 kinds of vital proteins associated with NF-κB and PKC pathways, could activate the basal activity of 5'LTR and IP promoters but inhibit the Tas-regulated activity of both promoters. Furthermore, PFV Tas was identified to trigger the transcription of the NF-κB promoter.

Conclusion: NF-κB had a negative effect on PFV 5'LTR and IP promoter activities, the PKC pathway might upregulate 5'LTR and IP promoter activities, and the JNK and NF-AT signal pathway could increase the Tas-regulated promoter activity of PFV 5'LTR. This study sheds light on the interaction between PFV and the host cell and may help utilize the viral promoters in retroviral vectors designed for gene transfer experiments.

Background: Host restriction factors are cellular proteins that inhibit specific steps of the viral life cycle. Since the 1970s, several new factors have been identified, including human immunodeficiency virus-1 (HIV-1) replication restriction. Evidence accumulated in the last decade has substantially broadened our understanding of the molecular mechanisms utilized to abrogate the HIV-1 life cycle.

Summary: In this review, we focus on the interaction between host restriction factors participating in the early phase of HIV-1 infection, particularly CA-targeting proteins. Host factors involved in the late phase of the replication cycle, such as viral assembly and egress factors, are also described. Additionally, current reports on well-known antiviral intrinsic factors, as well as other viral restriction factors with their emerging roles, are included.

Conclusion: A comprehensive understanding of the interactions between viruses and hosts is expected to provide insight into the design of novel HIV-1 therapeutic interventions.

Introduction: Hepatitis C virus (HCV) infection remains a major public health problem worldwide. In Burkina Faso, nearly 720,000 people are living with HCV, and each year about 900 people die from complications of cirrhosis or hepatocellular carcinoma. This study was planned to determine the HCV seroprevalence, characterize circulating genotypes, and monitor HCV viral loads in patients under treatment with antivirals.

Methods: A total of 4,124 individuals and 167 patients in the pre-therapy program were recruited. The "SD Bioline HCV" kit was used for rapid screening of anti-HCV antibodies. Viral load and genotyping were performed in 167 HCV patients on antivirals using the "Iontek HCV Quant" and "Iontek genotyping" kits.

Results: Prevalence of HCV was 1.65% (68/4,124), and the median viral load of participants was 5.37 log10/mL (1.32-7.67 log10/mL). Genotype 2 was predominant with a frequency of 86.23% (144/167) and appeared to be more active with higher viral load compared to 13.77% (23/167) for genotype 1 (p < 0.001). After 24 weeks of pan-genotypic direct-acting antivirals, such as sofosbuvir/daclatasvir and sofosbuvir/velpatasvir, the viral loads of all patients became undetectable.

Conclusion: The responses to antivirals by the circulating genotypes indicate that the results are very satisfactory. Therefore, the prevalence of HCV in the population can be reduced through identification of cases and treatment.

Introduction: Epstein-Barr virus (EBV/HHV-4) has been implicated in the pathogenesis of multiple sclerosis (MS). This study was conducted to investigate the levels of pro-inflammatory cytokines IL-1β and IL-6 in healthy EBV carriers and MS patients with prior EBV infection in response to treatment with EBV nuclear antigen 1 (EBNA-1) and replication and transcription activator (BRLF-1/Rta) peptide antigens in whole blood cell culture to assess the cytokine expression across all cells in the peripheral blood.

Methods: Isolated whole blood cells from the included participants were incubated at a concentration of 106 cells/mL with BRLF-1 or EBNA-1. The amount of IL-1β and IL-6 transcripts were measured with quantitative RT-PCR at day 3 after incubation. MTT assay was conducted to examine cytotoxicity of the peptides and their effect on cell viability. Changes in cytokine expression and cell viability were analyzed using one-way and two-way ANOVA, respectively.

Results: Ten MS patients and ten healthy donors were enrolled in the study. Treatment with the peptide antigens resulted in increased cytokines expression in both MS patients and healthy subjects. Furthermore, IL-1β levels were higher in MS patients compared to healthy EBV carriers. MTT assay revealed no significant difference in cell viability between the two groups.

Discussion: The higher levels of IL-1β in response to EBV antigens in MS patients may reflect the host neuroinflammatory environment and support the notion that immune response against EBV has a role as an aggravating factor in the progression of MS by contributing to the neuroinflammatory cascade.

Introduction: Hepatitis B virus (HBV) infection is a disease with high incidence and lack of effective treatment. In this study, we further explored the mechanism of resveratrol (RVT) in the inhibition of HBV replication. The effects of RVT on HBV replication were verified using in vitro and in vivo experiments.

Methods: HepG2 and HepG2.2.15 cell lines were cultured in vitro, and different concentrations of RVT were used to determine its effect on the proliferation of the two cell lines. Autophagy agonists and inhibitors were given, and whether RVT exerts its effect on the proliferation of HepG2 and HepG2.2.15 cells through autophagy was determined. Reverse transcription-quantitative polymerase chain reaction and Western blot were used to detect changes in autophagy-related factors LC3-II, LC3-I, Beclin 1, and p62. Through transfection of pmiR-155, shmiR-155, and the corresponding control group, the relevant mechanism of RVT in inhibiting the proliferation of HepG2 and HepG2.2.15 cells was analyzed. RVT inhibited the toxicity for HepG2.2.15 cells and reduced HBV replication in vitro (p < 0.05). This effect of RVT was enhanced by rapamycin (RAPA; autophagy activator; p < 0.05) but was partially reversed by 3-MA (autophagy inhibitor; p < 0.05). In addition, our results showed that miR-155 expression was higher in HepG2.2.15 cells than in HepG cells (p < 0.05). miR-155 expression in the RVT treatment group was significantly reduced (p < 0.05). We designed an miR-155 overexpression plasmid, low miR-155 expression plasmid, and the corresponding negative control for transfection and found that transfection of pmiR-155 can partially reverse the effect of RVT (p < 0.05), while transfection with shmiR-155 can enhance the effect of RVT (p < 0.05).

Discussion: RVT inhibits miR-155, activates autophagy, inhibits the toxicity for HepG2.2.15 cells, and reduces HBV replication, providing a new research direction for the treatment of HBV infection.

New kinds of HIV-1 circulating recombinant forms (CRFs) and unique recombinant forms (URFs) earn a great prevalence in China nowadays. In this study, we identified 2 similar URFs (2016GXNNIDU037 and 2019QZLSIDU253) both isolated from intravenous drug users (IDUs) in Guangxi, China. Phylogenetic analysis of the near full-length genome (NFLG) revealed 2 URFs both clustered with CRF01_AE but setting up a monophyletic branch, supporting a high bootstrap value. Bootscan analysis and subregional recombinant analysis found that the NFLG of 2016GXNNIDU037 and 2019QZLSIDU253 were both composed of CRF01_AE and CRF07_BC, with 3 CRF07_BC mosaic segments inserted into CRF01_AE backbones. The CRF01_AE segments of the 2 URFs clustered with a previously reported cluster 2 lineage of CRF01_AE. The 5 recombinant breakpoints of the 2 URFs were quite similar. Distinct from CRF01_AE/CRF07_BC URFs reported before, 2016GXNNIDU037 and 2019QZLSIDU253 are new evidence of a high genetic variety of HIV-1 in Guangxi, which may pose new challenges to HIV-1 prevention and molecular epidemiological surveillance in China.

Background: COVID-19 has emerged as the most serious pandemic in the 21st century to date. COVID-19 patients may develop various disease symptoms that hinder the accurate clinical diagnosis.

Summary: Routine diagnosis of COVID-19 requires complementary investigations, including computed tomography, immunological assays, and molecular assays like real-time RT-PCR, loop-mediated isothermal amplification, metagenomic next-generation sequencing, and clusters of regularly interspaced short palindromic repeats-based assays. Clinically approved antiviral drugs available for the COVID-19 treatment are very limited. The most common measurements that enhance health condition and patients' viability are conservation fluid management, oxygen therapy, and antibiotics. Several therapeutic options have been developed or repurposed to prevent virus replication and/or modulate the immune response against virus infection. These options include various drugs that affect virus entry and membrane fusion, inhibit polymerase and protease activity, suppress the host pro-inflammatory cytokines, and utilize cell therapy approaches.

Key messages: In this review, we aimed to provide an up-to-date discussion on the current diagnostic options and therapeutic strategies used to control and manage COVID-19 in clinical and point-of-care settings.

Introduction: Chronic fatigue syndrome (CFS) is a neurological disease that is accompanied by excessive fatigue or tiredness. There are several reports confirming the association between human herpesvirus 6 (HHV-6) infection and CFS illness. This systematic review and meta-analysis was performed to integrate the information of published studies with regard to this association until May 2021.

Methods: The literature search was based on keywords including "chronic fatigue syndrome and HHV 6," "chronic fatigue syndrome and HHV-6," "chronic fatigue syndrome and HHV6," "chronic fatigue syndrome and Herpes virus 6," and "chronic fatigue syndrome and Herpesvirus6" in MEDLINE (PubMed), Web of Science, and EMBASE.

Results: The literature search identified 17 studies to be included in the systematic review and 11 studies in meta-analysis. The symmetry funnel plot and Egger's test (p value = 0.2) identified no publication bias among studies. Moreover, the low level of I2 revealed homogeneity across studies.

Discussion: In conclusion, the association between the HHV-6 infection and CFS incidence was substantiated. However, the results of this study also suggest that further comprehensive studies are needed to solidify the association between HHV-6 and CFS. Future studies should consider additional factors that may have affected the significance of such a correlation.

Introduction: Chronic hepatitis B (CHB) is a major cause of chronic liver diseases and tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV) are recommended as primary treatments. This study aimed to evaluate the efficacy and safety of ETV, TDF, and TAF in a real-world clinical setting.

Methods: In this retrospective cohort study, a total of 363 CHB patients who were treated with ETV (n = 163), TDF (n = 154), or TAF (n = 46) from July 2007 to September 2019 were enrolled.

Results: Median patient age was 51 years and 66.4% of patients were male. Median duration of treatment with ETV, TDF, or TAF was 49.0 months (interquartile range, 27.0-74.0 months). In terms of safety, cholesterol was mildly increased in the ETV and TAF groups and significantly lowered in the TDF group than baseline (p < 0.001). There was no significant difference in liver cirrhosis-related complications among the 3 groups at 48 weeks (p = 0.235). Hepatitis B e antigen seroconversion, complete virological response, and alanine aminotransferase normalization at 48 weeks as measures of treatment efficacy were not significantly different among the 3 groups (p = 0.142, 0.538, and 0.520, respectively). There was also no significant difference in cumulative incidence rate of hepatocellular carcinoma (HCC) between the ETV and TDF groups (p = 0.894).

Conclusions: ETV, TDF, and TAF were safe antiviral agents and showed similar antiviral effect for CHB at 48 weeks. Cirrhosis-related complications and annual HCC incidence rates did not differ significantly between the ETV and TDF groups over the 48 week follow-up period.

Introduction: Virus-like particles (VLPs), self-assembled multiprotein structures, can stimulate robust immune responses due to their structural similarity to native virions that allow the presentation of multiple copies of the target epitopes. Utilizing VLPs as vaccine platforms to present exogenous antigens is a promising and challenging approach in the vaccine development field. This study investigates the potential of the truncated hepatitis E virus (HEV) capsid as a VLP platform to present foreign antigens.

Methods: The S and M domains of the HEV capsid protein were selected as the optimal carrier (CaSM). The exogenous antigen Seq8 containing 3 neutralizing epitopes from 3 different foot-and-mouth disease virus (FMDV) strains was linked to the C-terminal of CaSM to construct a chimeric VLP (CaSM-Seq8). The chimeric particles were produced in Escherichia coli, and their morphology, physicochemical properties, antigenicity, and immunogenicity were analyzed.

Results: Morphological analysis showed that CaSM-Seq8 self-assembled into VLPs similar to CaSM VLPs (∼26 nm in diameter) but smaller than native HEV virions. Further, the thermal stability and the resistance to enzymatic proteolysis of Seq8 were enhanced when it was attached to the CaSM carrier. The antigenicity analysis revealed a more robust reactivity against anti-FMDV antibodies when Seq8 was presented on CaSM particles. Upon injection into mice, FMDV-specific IgGs induced by CaSM-Seq8 appeared earlier, increased faster, and maintained higher levels for a longer time than those induced by Seq8 alone or the inactivated FMDV vaccine.

Conclusion: This study demonstrated the potential of utilizing the truncated HEV capsid as an antigen-presenting platform for the development of chimeric VLP immunogens.