ABSTRACT
Herpes simplex virus type 1 (HSV-1) had led to kinds of clinical disorders and became an important cause of morbidity and mortality worldwide, such as herpetic gingivostomatitis in children. Previous studies reported that HSV-1 infection is common and has evolved a variety of mechanisms to evade the immune system, such as dysregulation of miRNAs. However, reports concerning the role of miRNA in HSV-1infection are limited. Here, we report that a host microRNA, miR-373, was significantly upregulated by HSV-1 infection in Hela cells and patients with herpetic gingivostomatitis and it facilitated HSV-1 replication in vitro. Subsequently, we demonstrated that miR-373 was a negative regulator of IFN-I response by directly targeting IRF1, resulting in the suppression of interferon stimulated gene (ISG) expression and enhancement of HSV-1 infection. Taken together, our findings provide new evidence of which HSV-1 hijacks the host miRNAs to promote its replication by negatively regulating the production of type I IFN and suggest a novel potential anti-HSV-1 therapeutic target.
Subject(s)
Herpesvirus 1, Human/physiology , Interferon Regulatory Factor-1/genetics , MicroRNAs/genetics , Virus Replication/genetics , Animals , Case-Control Studies , HeLa Cells , Humans , Interferon Type I/metabolism , Mice , Rats , Stomatitis, Herpetic/genetics , Stomatitis, Herpetic/virology , Up-RegulationABSTRACT
BACKGROUND: Apolipoprotein E is polymorphic in the human population. APOE4 has previously been reported to correlate with symptomatic oral and genital herpes disease. METHODS: APOE was genotyped in 182 subjects with herpes simplex virus (HSV) 2 and in 62 subjects with HSV-1, including 44 subjects with both viral types for a total of 200 adults. HSV shedding was measured by PCR from swab samples obtained daily from mucosa for at least 30 days. Participants also maintained a diary of oral or genital lesions. RESULTS: The APOE genotypes observed reflected the US white population and the Hardy-Weinberg equilibrium. Genital and oral HSV shedding was detected on 17.2% and 3.7% of overall days, respectively, whereas genital and oral lesion rates were 10.1% and 2.9%. Using Poisson regression and adjusting for known correlates of HSV shedding, a significant association was not observed between the APOE genotype and genital or oral HSV shedding, or genital HSV lesions. However, the presence of the APOE4 allele was associated with a higher rate of oral herpetic lesions, with a relative risk of 4.64 (95% CI 1.32 to 15.05, p=0.016). CONCLUSIONS: Variation at the APOE locus may be associated with clinical manifestations of HSV-1 infection, but does not appear to correlate with herpes simplex viral reactivation in humans.
Subject(s)
Apolipoproteins E/genetics , Herpes Genitalis/genetics , Herpesvirus 1, Human/genetics , Herpesvirus 2, Human/genetics , Stomatitis, Herpetic/genetics , Adult , Antibodies, Viral/analysis , DNA, Viral/analysis , Enzyme-Linked Immunosorbent Assay , Female , Gene Frequency , Genotype , Herpes Genitalis/virology , Herpesvirus 1, Human/physiology , Herpesvirus 2, Human/physiology , Humans , Male , Polymerase Chain Reaction , Prognosis , Stomatitis, Herpetic/virology , Toll-Like Receptor 2/genetics , Virus SheddingABSTRACT
A 12-year-old daughter of consanguineous Moroccan parents was diagnosed with cyclic neutropenia, based on a combination of recurrent gingivostomatitis, a fluctuating neutrophil count, and several episodes of severe neutropenia. No ELA2 gene mutations were found. At age 19 years she presented with edema of the limbs, proteinuria and renal failure. Renal amyloidosis AA was diagnosed by biopsy. Gene mutations associated with family Mediterranean fever (FMF) were sought, and a homozygous mutation (M694V) was found in the MFEV gene. This is the novel finding of FMF that masqueraded as cyclic neutropenia.
Subject(s)
Familial Mediterranean Fever/diagnosis , Familial Mediterranean Fever/genetics , Familial Mediterranean Fever/physiopathology , Neutropenia/pathology , Adult , Amyloidosis/genetics , Child , Chronic Disease , Cytoskeletal Proteins/genetics , DNA Mutational Analysis , Diagnosis, Differential , Female , Fever/genetics , Humans , Kidney Diseases/genetics , Mutation , Pyrin , Stomatitis, Herpetic/geneticsABSTRACT
Chromosomal breakage and sister-chromatid exchanges (SCE) were studied in peripheral lymphocytes of 9 patients with primary herpetic stomatitis (PHS), 12 patients with secondary herpetic stomatitis (SHS) and 12 controls. The incidence of chromosomal breakage was significantly higher in PHS patients (mean 23%, P. = 0.0002) and in SHS patients (mean 20.25%, P. = 0.0003) compared to the controls (mean 4.2%). The incidence of SCE per 46 chromosomes was significantly higher in SHS patients (mean 16.564) compared with (P. less than 0.001) the controls (mean 11.367) and compared with (P. = 0.006) the PHS patients (mean 12.131). It is concluded that both PHS and SHS patients exhibit structural chromosomal damage; SHS patients in addition exhibit more repaired chromosomal lesions.
