Murine nasal-associated lymphoid tissue (NALT) harbors human alphaherpesvirus 1 (HSV-1) DNA during latency, and dexamethasone triggers viral replication.
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引用次数: 0
Abstract
Human alphaherpesvirus 1 (HSV-1) acute infection causes conjunctivitis, encephalitis, genital lesions, and herpes esophagitis. Following acute infection, HSV-1 and other alpha-herpesvirinae subfamily members establish life-long latency in neurons within the trigeminal ganglia and central nervous system. Notably, certain animal alpha-herpesvirinae subfamily members, including bovine alphaherpesvirus 1 (BoHV-1), canine herpesvirus 1, equine herpesvirus 4, and pseudorabies virus, establish a quiescent/latent infection in tonsils. BoHV-1 viral gene expression and virus shedding from tonsils also occur during reactivation from latency in calves. Consequently, we tested whether nasopharyngeal lymphoid tissue (NALT) harbors HSV-1 DNA in latently infected mice because it is structurally and functionally comparable with tonsils. NALT prepared from latently infected mice consistently contained viral DNA, but infectious virus was not detected. In contrast to latently infected TG neurons, the HSV-1 latency-associated transcript was not detected in NALT of latently infected mice. HSV-1 DNA levels, immediate early RNA expression, and virus shedding were readily detected when NALT explants were cultured with a medium containing the synthetic corticosteroid dexamethasone for 48 h. Increased viral DNA and virus production were not detected in NALT explants when incubated with a medium lacking dexamethasone. Sorting cells from NALT of HSV-1 latently infected mice revealed that dendritic cells, microfold cells, and natural killer cells, but not B or T cells, harbor HSV-1 DNA, and infectious virus was readily detected when cultured in medium containing dexamethasone. In summary, certain NALT cells consistently contain viral DNA in latently infected mice, and dexamethasone triggers viral gene expression and virus production.
Importance: Human alphaherpesvirus 1 (HSV-1) acute infection causes various diseases, including herpes esophagitis. HSV-1 subsequently establishes lifelong latency in neurons within the trigeminal ganglia and central nervous system. Viral DNA, but not infectious virus, was consistently detected in nasopharyngeal lymphoid tissue (NALT) of latently infected mice. NALT is structurally and functionally comparable with the tonsils of other mammals, including humans. RNA and protein expression of infected cell protein 0 (ICP0) and ICP4 plus virus production were consistently detected when NALT explants were cultured with a medium containing dexamethasone, a synthetic corticosteroid. Sorting NALT cells from HSV-1 latently infected mice revealed dendritic cells, microfold cells, and natural killer cells that harbor HSV-1 DNA. Virus shedding was readily detected when viral DNA-positive NALT cells were cultured in a medium containing dexamethasone. These studies revealed that specific NALT cells harbor viral DNA, and dexamethasone triggered viral replication and virus production, suggesting that reactivation from a latent or quiescent infection had occurred.
期刊介绍:
Journal of Virology (JVI) explores the nature of the viruses of animals, archaea, bacteria, fungi, plants, and protozoa. We welcome papers on virion structure and assembly, viral genome replication and regulation of gene expression, genetic diversity and evolution, virus-cell interactions, cellular responses to infection, transformation and oncogenesis, gene delivery, viral pathogenesis and immunity, and vaccines and antiviral agents.