UL7, a tegument protein of Herpes Simplex Virus type I (HSV-1), is highly conserved in viral infection and proliferation and has an unknown mechanism of action. A HSV-1 UL7 mutant (UL7-MU) was constructed using the CRISPR-cas9 system. The replication rate and plaque morphology were used to analyze the biological characteristics of the wild-type (WT), UL7-MU and MU-complemented P1 viruses. The virulence of the viruses was evaluated in mice. Real-time RT-qPCR and ChIP assays were used to determine the expression levels of relevant genes. The replication capacity of a recombinant virus (UL7-MU strain) was 10-fold lower than that of the WT strain. The neurovirulence and pathologic effect of the UL7-MU strain were attenuated in infected mice compared with the WT strain. In the latency model, the expression of latency-associated transcript (LAT) in the central nervous system (CNS) and trigeminal nerve was lower in UL7-MU-infected mice than in WT strain-infected mice. The transcription level of the immediate-early gene α-4 in UL7-MU-infected cells was reduced by approximately 2-fold compared with the clear transcriptional peak identified in WT strain-infected Vero cells within 7 h post-infection (p.i.). By modulating the transcription of the α-4 gene, UL7 may be involved in transcriptional regulation through its interaction with the transcript complex structure of the viral genome during HSV-1 infection.

Herpes simplex virus type 1 (HSV-1), one of the human pathogens widely epidemic and transmitted among various groups of people in the world, often causes symptoms known as oral herpes or lifelong asymptomatic infection. HSV-1 employs many sophisticated strategies to escape host antiviral immune response based on its multiple coding proteins. However, the functions involved in the immune evasion of miRNAs encoded by HSV-1 during lytic (productive) infection remain poorly studied. Dual-luciferase reporter gene assay and bioinformatics revealed that Asp-Glu-Ala-Asp (DEAD)-box helicase 41 (DDX41), a cytosolic DNA sensor of the DNA-sensing pathway, was a putative direct target gene of HSV-1-encoded miR-H2-3p. The transfection of miR-H2-3p mimics inhibited the expression of DDX41 at the level of mRNA and protein, as well as the expression of interferon beta (IFN-β) and myxoma resistance protein I (MxI) induced by HSV-1 infection in THP-1 cells, and promoted the viral replication and its gene transcription. However, the transfection of miR-H2-3p inhibitor showed opposite effects. This finding indicated that HSV-1-encoded miR-H2-3p attenuated cytosolic DNA–stimulated antiviral immune response by manipulating host DNA sensor molecular DDX41 to enhance virus replication in cultured cells.

Aims: Inflammation is a pivotal characteristic of neurodegenerative diseases. The triggering receptor expressed on the myeloid cells 2 (TREM2) gene has previously been shown to suppress inflammation by directly inhibiting inflammation-related pathways. Mitochondrial dysfunction has recently emerged as another critical pathological manifestation of neurodegenerative diseases. Although TREM2 is involved in the regulation of cellular energy metabolism and mitochondrial autophagy, its role in the relationship between inflammation and mitochondrial autophagy remains unclear. Methods: In this study, we generated TREM2-overexpressing BV-2 cells and established a neuroinflammatory model with LPS. We compared these cells with wild-type cells in terms of inflammation, metabolism, autophagy, and mitochondria using methods such as RT–qPCR, Western blotting, immunocytochemistry, transmission electron microscopy, and flow cytometry. Results: Microglia overexpressing TREM2 exhibited increased resistance to inflammation. Additionally, these cells inhibited the metabolic reprogramming that occurs early in LPS-induced inflammation, reduced ROS release, mitigated mitochondrial damage, maintained a certain level of autophagic activity, and cleared damaged mitochondria. Consequently, they alleviated the inflammation caused by the mitochondrial barrier. Conclusions: ur results suggest that TREM2 can alleviate inflammation by maintaining cellular metabolic homeostasis and mitochondrial autophagy activity.

As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1.Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post‐infection,and viral latency‐associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG)on day 365 post‐infection. Neutralization testing and enzyme‐linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.

Herpes simplex virus type 1(HSV-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. Some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of these has achieved a valid epidemiological protective efficacy in the human population. In the present study, we constructed an attenuated HSV-1 strain M3 through the partial deletion of UL7, UL41, and the latency-associated transcript (LAT) using the CRISPR/Cas9 system. The mutant strain exhibited lowered infectivity and virulence in macaques. Neutralization testing and ELISpot detection of the specific T-cell responses confirmed the specific immunity induced by M3 immunization and this immunity defended against the challenges of the wild-type strain and restricted the entry of the wild-type strain into the trigeminal ganglion. These results in rhesus macaques demonstrated the potential of the attenuated vaccine for the prevention of HSV-1 in humans.

Herpes simplex virus type 1 (HSV-1), an α subgroup member of the human herpesvirus family, infects cells via the binding of its various envelope glycoproteins to cellular membrane receptors, one of which is herpes virus entry mediator (HVEM), expressed on dendritic cells. Here, HVEM gene-deficient mice were used to investigate the immunologic effect elicited by the HSV-1 infection of dendritic cells. Dendritic cells expressing the surface marker CD11c showed an abnormal biological phenotype, including the altered transcription of various immune signaling molecules and inflammatory factors associated with innate immunity after viral replication. Furthermore, the viral infection of dendritic cells interfered with dendritic cell function in the lymph nodes, where these cells normally play roles in activating the T-cell response. Additionally, the mild clinicopathological manifestations observed during the acute phase of HSV-1 infection were associated with viral replication in dendritic cells.