Journal of Medical Virology最新文献

HEV infection has become a global health concern. The study of HEV pathogenicity has been hindered by the lack of a suitable in vitro culture system. In the present research, we systematic demonstration of efficient replication of swine GT4 HEV in A549 cells, Huh-7 cells, and HepG2/C3A cell lines. The results of the immunofluorescence assay and immunofluorescence confocal assay showed that swine GT4 HEV is efficiently replicated in three cell lines at 72 h postinoculation. Meanwhile, we also detected the virus titer quantified were increased at 2-, 6,- and 11-days postinoculation. Moreover, we successfully observed HEV virus particles in the cell suspension at 6 days postinoculation. This finding holds significance for advancing in vitro HEV studies.

Nanoparticles are rapidly becoming the method of choice for a number of nanomedicine applications, especially drug delivery. Many current nanoparticle models for drug delivery include a metal base with a drug conjugated to its surface. However, this raises concerns regarding toxicity since the conjugated drug and metal-based center of the nanoparticle are generally not biocompatible. A novel approach to solve this dilemma is the development of nanosized biocompatible polymer-based micellar nanoparticles (MNPs), created from methoxy poly(ethylene-glycol) poly(ɛ-caprolactone)-methoxy poly(ethylene glycol) (i.e., mPEG-PCL-mPEG) triblock polymers formed around an antiviral drug of choice, ribavirin. The goal is to create a drug carrier triblock nanoparticle system that is labile at a specific intercellular pH resulting in drug release, leading to the suppression of viral pathogens, and without undue toxicity to the cell. Through this approach we created a drug-loaded nanoparticle that dissociates when exposed to pH of 5.49 (endosomal pH), releasing ribavirin intercellularly, resulting in effective suppression of the mosquito-borne virus, Zika, in JEG-3 cells (gestational choriocarcinoma cells), in comparison to untreated and unencapsulated ribavirin controls as shown by plaque reduction assays and confirmation by RT-PCR. The level of suppression observed by ribavirin-loaded MNPs was achieved while requiring approximately 90% less ribavirin than in experiments utilizing unencapsulated ribavirin. The drug delivery system that is described here has shown significant suppression of Zika virus and suggests a role for this drug delivery system as an antiviral platform against additional viral pathogens.

We looked at the interactions between viral loads, coinfection rates and disease severity for children infected with two pneumoviruses: human metapneumovirus (HMPV) and respiratory syncytial virus (RSV). The HMPV RNA load in nasopharyngeal swabs of hospitalized children was significantly higher in mono-infections compared to coinfections but this was not the case for RSV, which could be explained by different innate immune responses. Also, the viral load of neither of the two viruses was associated with disease severity although RSV-infected children had higher severity scores than HMPV-infected children.

Severe fever with thrombocytopenia syndrome (SFTS), a tick-borne infectious disease caused by the SFTS virus (SFTSV), is becoming a significant public health threat due to its high mortality rate. Knowledge of SFTSV in southeastern coastal China is limited. The whole genomes of 66 SFTSV strains collected from 2013 to 2023 in Hangzhou, a coastal city in China, were amplified and sequenced to elucidate the geography-related genetic and pathogenic diversity. Hangzhou SFTSVs could be classified into five pure genotype groups (A, B-2, D, E, and F); genotype A was dominant, and genotype E was significantly associated with SFTS fatality. An unclassified sublineage of the L segment was proposed as a novel B-4 subgenotype. Seven types of genetic reassortants (abbreviated as B-3B-3B-1, CCA, B-2AB-2, B-2CB-2, DFD, B-4FF, and B-4B-2B-1 for the L, M, and S segments) were identified, including three novel forms. Six recombination events and ten amino acid substitutions were identified in the Hangzhou viruses. Collectively, our results demonstrated that all known SFTSV genotypes co-circulated in Hangzhou, leading to a gradual increase in genetic diversity and the generation of novel reassortants. Increased surveillance is urgently needed in Hangzhou, a critical region for SFTSV genetic exchange.

The hepatitis E virus (HEV) is an important causative agent of acute hepatitis (AH). Despite reports of human infection in Brazil, the investigation is not routinely conducted, even in cases of elevated liver enzymes. This study evaluated two groups: group 1—patients with acute hepatitis A (n = 44); group 2—patients with nonA-C AH (n = 47). They were tested by enzyme immunoassay for anti-HEV IgM/IgG and real-time PCR for HEV RNA detection. The positive sample for HEV RNA was submitted for sequencing. The seroprevalence of anti-HEV IgM and IgG in group 1 was 4% (2/44) and 14.5% (7/44), respectively. Viral RNA was not detected in any sample. In group 2, the anti-HEV IgM positivity was 4.3% (2/47), and IgG 14.9% (7/47). RNA was detectable in one case, which presented a viral load of 222.4 IU/μL and positive anti-HEV IgM/IgG. In the phylogenetic analysis, the genotype identified was HEV-3f. These results indicate that HEV infection should be considered a possible diagnosis in cases of non-A–C AH. The patient identified with acute hepatitis E had recently traveled to the Northeast region of Brazil (Garanhuns city in Pernambuco state), where there are reports of high HEV seroprevalence among pigs. The close phylogenetic relationship observed between the sequence characterized in this study and strains isolated from pigs in nearby cities where the patient went suggested a possible zoonotic transmission in this region. This study highlights the importance of expanding studies and improving surveillance to understand better and manage HEV infections nationwide.

Kidney transplant recipients (KTRs) are highly vulnerable to COVID-19. An intensified scheme of vaccination offers short-term protection to the 50%–75% of KTRs able to develop a germinal center reaction, required for the generation of neutralizing titers of antibodies (NAbs). However, the duration of this vaccinal protection is unknown. In-depth longitudinal analysis of the immune response to vaccination of 33 KTRs demonstrates that the low peak of IgGs, the progressive decline in antibody titers, and the emergence of a variant of concerns (VOC) of SARS-CoV2, synergize to let 2/3 of responders to vaccine without NAbs after only a few months. Yet, a retrospective study of an independent cohort of 274 KTRs, revealed that the risk of severe COVID-19 in the latter was low, similar to that of patients with serum neutralizing capacity against VOC. Our work links this late vaccine protection with the presence of memory B cells, which are generated during the initial vaccine-induced germinal center reaction, have a wide repertoire directed against conserved spike epitopes, and rapidly differentiate into IgG-producing plasma cells upon antigenic rechallenge. We conclude that in contrast with a serological layer that goes fading rapidly, the cellular layer of humoral memory provides an efficient long-term protection against VOC to KTRs. This illustration of the complementary roles of the two layers of the humoral memory has implications in immunopathology beyond the COVID-19 in KTRs.