Frontiers in virology最新文献

The past decade has seen the global reemergence and rapid spread of enterovirus D68 (EV-D68), a respiratory pathogen that causes severe respiratory illness and paralysis in children. EV-D68 was first isolated in 1962 from children with pneumonia. Sporadic cases and small outbreaks have been reported since then with a major respiratory disease outbreak in 2014 associated with an increased number of children diagnosed with polio-like paralysis. From 2014-2018, major outbreaks were reported every other year in a biennial pattern with > 90% of the cases occurring in children under the age of 16. With the outbreak of SARS-CoV-2 and the subsequent COVID-19 pandemic, there was a significant decrease in the prevalence EV-D68 cases along with other respiratory diseases. However, since the relaxation of pandemic social distancing protocols and masking mandates the number of EV-D68 cases have begun to rise again-culminating in another outbreak in 2022. Here we review the virology, pathogenesis, and the immune response to EV-D68, and discuss the epidemiology of EV-D68 infections and the divergence of contemporary strains from historical strains. Finally, we highlight some of the key challenges in the field that remain to be addressed.

Heart disease is the leading cause of death worldwide. Myocarditis, or inflammation of the cardiac muscle, is estimated to cause up to 1.5 million cases annually, with viral infection being the most common disease culprit. Past studies have shown that Parvovirus B19 is routinely detected in endomyocardial biopsies. This virus has been linked to acute heart inflammation, which can cause cardiac muscle damage. However, because Parvovirus B19 can be found in the heart tissues in the absence of disease symptoms, it is unclear if the long-term presence of the virus contributes to, or initiates, heart disease. Here, we utilized a PCR-based detection assay to assess the presence of the B19V genome and its mRNA intermediates in human heart tissues. The analysis was carried out in three heart layers derived from one individual: epicardium, endocardium and myocardium. We showed the Parvovirus B19 genome presence variability in different heart layers. Similarly, viral transcriptional activity, assessed by the mRNA presence, was detected only in a few of the analyzed samples. Our results suggest that localized sites of Parvovirus B19 infection may exist within individual heart layers, which may have implication for the cardiac muscle inflammation.

The human family of APOBEC3 enzymes are primarily studied as single-stranded DNA deoxycytidine deaminases that act as host restriction factors for a number of viruses and retroelements. The deamination of deoxycytidine to deoxyuridine causes inactivating mutations in target DNA and the nucleic acid binding ability may also cause deamination independent restriction. There are seven APOBEC3 enzymes in humans, named A-H, excluding E, each of which has restriction activity against a subset of viruses or retroelements. There are primarily four, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H that have been found to restrict replication of HIV-1, however their restriction activity varies and they have primarily been studied individually despite co-expression in the cells that HIV-1 infects. It is known that APOBEC3F hetero-oligomerizes with APOBEC3G and APOBEC3H and that this influences host restriction outcomes during HIV-1 infection in tissue culture. Here, we examined if APOBEC3F interacts with APOBEC3D and the functional outcomes. We found that APOBEC3D mRNA expression was similar to or higher than APOBEC3F mRNA in multiple donors, suggesting that the proteins would be co-expressed, allowing for interactions to occur. We determined that APOBEC3F and APOBEC3D interacted primarily through an RNA intermediate; however, this interaction resulted in APOBEC3D competitively excluding APOBEC3F from virions. Although HIV-1 restriction still occurred when APOBEC3F and APOBEC3D were co-expressed, it was due to primarily APOBEC3D-mediated deamination-independent restriction. The APOBEC3D-mediated exclusion of APOBEC3F from HIV-1 encapsidation could be recapitulated in vitro through RNA capture experiments in which APOBEC3D decreased or abrogated the ability of APOBEC3F to bind to HIV-1 protease or 5’UTR RNA, respectively. Overall, the data suggest that there are mechanisms at the protein level that segregate APOBEC3s into different virus particles.

Mayaro (MAYV) and Una (UNAV) are emerging alphaviruses circulating in the Americas. Earlier reports have revealed that MAYV infects different human cell lines, including synovial and dermal fibroblasts, chondrocytes, osteoblasts, astrocytes and pericytes, as well as neural progenitor cells. In this study we evaluated the susceptibility of immortalized human microglia HMC3 cells and brain microvascular endothelial HBEC-5i cells to MAYV and UNAV infection. Cytopathic effects, cell viability, viral progeny yields, and the presence of E1 and nsP1 proteins in HMC3 and HBEC-5i cells infected with several MAYV or UNAV strains were assessed using an inverted microscope, MTT assay, plaque-forming assays, and immunofluorescence or Western blot, respectively. Finally, the expression of immune response genes was analyzed using RT-qPCR. MAYV and UNAV demonstrated strong cytopathic effects and significantly reduced cell viability in HMC3 cells. Moreover, the HMC3 cells were efficiently infected regardless of the virus strain tested, and E1 and nsP1 viral proteins were detected. In contrast, only MAYV appeared to infect HBEC-5i cells, and minimal effects on cell morphology or viability were observed. Furthermore, the MAYV titer and viral protein levels were substantially lower in the infected HBEC-5i cells when compared to those of the infected microglia cells. Finally, unlike UNAV, MAYV elicited a strong expression of specific interferon-stimulated genes in microglia cells, along with pro-inflammatory cytokines implicated in the immune response. Collectively, these findings demonstrate that MAYV and UNAV are capable of infecting relevant human brain cells.

Hepatitis E viruses (HEV) Open Reading Frame 1 (ORF1) encodes a non-structural polyprotein. In most positive-sense RNA viruses found in animals, this non-structural polyprotein is cleaved by viral protease or host protease. However, the mechanism behind the processing of HEV polyprotein remains one of the most controversial questions in HEV biology. The role of putative HEV protease in processing is difficult to demonstrate. Recent studies have questioned the existence of HEV protease and suggested that pORF1 lacks protease activity. Conversely, studies also suggested the role of host proteases involved in the blood coagulation cascade, like thrombin, in processing the HEV pORF1 polyprotein. In summary, recent studies support the notion that pORF1 lacks protease activity and host proteases are responsible for processing pORF1. The present review compiles a thorough overview of contentious research on HEV’s papain-like cysteine protease (PCP) and highlights recent advancements in the field. We aim to discuss the challenges and opportunities in the field to focus on further research.

The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) family consists of cytosine deaminases implicated in diverse and important biological functions. APOBEC3 (A3) proteins belong to the APOBEC/AID family, and they catalyze the deamination of cytosine to uracil in single-stranded DNA and, to a lesser extent, in RNA substrates. In humans, seven A3 genes have been identified (A3A, A3B, A3C, A3D, A3F, A3G, and A3H). The introduction of lethal G-to-A or C-to-U mutations into certain viral genomes leads to virus inactivation. However, the mutagenic capability of A3 proteins could serve as a source of mutations to drive virus evolution. Therefore, recent studies have implied the role of A3 proteins in aiding the evolution of viruses, conferring them with severe manifestations such as drug resistance and/or immune evasion. In this review, we discuss in depth the interactions of A3 proteins with viruses that infect humans and our self-proteins.