Persistence of Herpes Simplex Virus Type 1 DNA in Chronic Conjunctival and Eyelid Lesions of Mice

Maggs, David J.; Chang, Ed; Nasisse, M P; Mitchell, William J.

doi:10.1128/jvi.72.11.9166-9172.1998

Cited by 44 publications

(17 citation statements)

References 34 publications

(51 reference statements)

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“…PRV DNA was consistently detected in some studies (5,9,35,36) but not others (3,18). Nonneural sites for latency or persistence have also been described for HSV-1 (8,17,29) and may be important for ocular disease (17). Thus, nonneural sites of latency or persistence may be a normal outcome of acute infection by certain ␣-herpesviruses.…”

Section: Discussionmentioning

confidence: 98%

“…Canine herpesvirus 1 DNA has been detected in tonsils of latently infected dogs (6), and during reactivation virus was recovered from tonsil tissues (20). HSV-1 has been detected in bone marrow of humans (8) and in other nonneural sites in small-animal models (17,29). Pseudorabies virus (PRV) DNA has also been detected in tonsils (2,3,16,35,36) of latently infected swine.…”

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confidence: 99%

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Persistence and Reactivation of Bovine Herpesvirus 1 in the Tonsils of Latently Infected Calves

Winkler¹,

Doster²,

Jones³

2000

J. Virol.

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Bovine herpesvirus 1 (BHV-1), like other members of the Alphaherpesvirinae subfamily, establishes latent infection in sensory neurons. Reactivation from latency can occur after natural or corticosteroid-induced stress culminating in recurrent disease and/or virus transmission to uninfected animals. Our previous results concluded that CD4 ؉ T cells in the tonsil and other adjacent lymph nodes are infected and undergo apoptosis during acute infection (M. T. Winkler, A. Doster, and C. Jones, J. Virol. 73:8657-8668, 1999). To test whether BHV-1 persisted in lymphoreticular tissue, we analyzed tonsils of latently infected calves for the presence of viral DNA and gene expression. BHV-1 DNA was consistently detected in the tonsils of latently infected calves. Detection of the latency-related transcript (LRT) in tonsils of latently infected calves required nested reverse transcription-PCR (RT-PCR) suggesting that only a few cells contained viral DNA or that LRT is not an abundant transcript. bICP0 (immediate-early and early transcripts), ribonucleotide reductase (early transcript), and glycoprotein C (late transcript) were not detected by RT-PCR in latently infected calves. When reactivation was initiated by dexamethasone, bICP0 and ribonucleotide reductase transcripts were detected.Following dexamethasone treatment, viral nucleic acid was detected simultaneously in trigeminal ganglionic neurons and lymphoid follicles of tonsil. LRT was detected at 6 and 24 h after dexamethasone treatment but not at 48 h. Dexamethasone-induced reactivation led to apoptosis that was localized to tonsillar lymphoid follicles. Taken together, these findings suggest that the tonsil is a site for persistence or latency from which virus can be reactivated by dexamethasone. We further hypothesize that the shedding of virus from the tonsil during reactivation plays a role in virus transmission.

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Persistence and Reactivation of Bovine Herpesvirus 1 in the Tonsils of Latently Infected Calves

Winkler¹,

Doster²,

Jones³

2000

J. Virol.

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“…We next studied the effect of HSV DNA on TLR gene expression in corneal cells, because HSV DNA is detected in patient corneas even in the chronic or silent stages of infection. In this experiment, we used McKrae and MP DNA, because both strains are pathogenic in the cornea (Wander et al, 1980;Centifanto-Fitzgerald et al, 1982) and KOS DNA does not persist long in HSK corneas (Maggs et al, 1998). When HCEs were transfected with McKrae or MP DNA, gene expression of TLR-3 was enhanced by 3?7 and 226, respectively, compared with untransfected cells (Fig.…”

Section: Induction Of Tlr-3 and -9mentioning

confidence: 99%

Herpes simplex virus 1 (HSV-1) DNA and immune complex (HSV-1–human IgG) elicit vigorous interleukin 6 release from infected corneal cells via Toll-like receptors

Hayashi

Hooper

Chin

et al. 2006

Journal of General Virology

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Toll-like receptor 3 (TLR-3) and TLR-9 gene expression and interleukin 6 (IL-6) secretion were studied in corneal cells with components of herpes simplex virus (HSV). Human corneal epithelial cells (HCEs) and primary human corneal fibroblasts (HCRFs) were infected with live HSV or UV-inactivated HSV (UV-HSV), transfected with HSV DNA or treated with HSV-anti-HSV IgG immune complexes. Gene expression of TLR-3 and -9 was analysed by real-time PCR. Supernatants were assayed for IL-6 by ELISA. Incubation of HCEs and HCRFs with live HSV-1, UV-HSV and HSV DNA resulted in augmented TLR-3 and -9 gene expression and IL-6 release. Moreover, infected or transfected HCRFs released greater amounts of IL-6 than did HCEs. As virus is frequently in the form of neutralized virus immune complexes, the ability of these immune complexes to interact with TLRs and trigger IL-6 production was evaluated. Here, it is shown that HSV-anti-HSV IgG complexes were as potent as HSV DNA in their ability to induce IL-6. Treatment of HCRFs transfected with HSV DNA with the TLR-9-inhibitory oligomer iODN, anti-TLR-3 antibody or phosphatidylinositol 3-kinase inhibitor indicated that IL-6 release from HCRFs was mediated by TLR-3 and -9 gene expression. These results demonstrated that neutralized HSV immune complexes were as potent as HSV DNA in enhancing IL-6 release from corneal fibroblasts. These phenomena were mediated via augmented TLR-3 and -9 gene expression. INTRODUCTIONCorneal herpes infection continues to cause blindness, especially in developed countries, and the disease still constitutes a major cause of corneal blindness rated second to trauma in the United States (Kaye et al., 2000;Xu et al., 2002). Corneal herpes infection elicits a robust inflammatory response and eventually leads to a vision-threatening stromal keratitis as a sequela of frequent reactivation of latent virus from the trigeminal ganglion (Doymaz & Rouse, 1992;Streilein et al., 1997). Although there are effective antiviral drugs to treat acute virus replication in the corneal epithelium, the effective management of host inflammatory responses requires the use of an immunosuppressant, such as a steroid, to keep the affected cornea clear (Wilhelmus et al., 1994;Sudesh & Laibson, 1999). The aetiology of herpetic stromal keratitis (HSK) is thought to be an aberrant Th1 cytokine-mediated immunopathology (Niemialtowski & Rouse, 1992;Thomas & Rouse, 1997;Verjans et al., 1998). Stromal haze continues to increase and becomes a problem following acute virus replication. In this situation, the precise disease-triggering and/or driving mechanism(s) are still largely unknown.Toll-like receptors (TLRs) are a family of evolutionarily conserved molecules that initially recognize pathogenassociated molecular patterns of invading microbes and trigger the initial host innate immune response. As a consequence, inflammatory cytokines are released (Takeda et al., 2003;Akira & Takeda, 2004;Iwasaki & Medzhitov, 2004;Netea et al., 2004). Among them, IL-6 is a critical cytokine component of cor...

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“…60 In a mouse model, viral replication was shown to be necessary for the development of HSK, 60 and, in other studies, HSV-1 was found to persistently infect the conjunctiva, eyelid skin, and cornea of mice. 61,62 In cats with FHV-1-induced stromal keratitis, Nasisse et al 63 observed the presence of viral antigen and infiltrating mononuclear cells in the corneal stroma, compatible with an immunopathologic mechanism.…”

Section: Prevalence Of Fhv-1mentioning

confidence: 99%

Prevalence of Chlamydophila felis and Feline Herpesvirus 1 in Cats with Conjunctivitis in Northern Italy

Rampazzo

Appino

Pregel

et al. 2003

Veterinary Internal Medicne

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The prevalence of Chlamydophila felis and feline herpesvirus 1 (FHV-1) infection in cats with conjunctivitis in northern Italy was investigated by conventional polymerase chain reaction (PCR) testing. In cats with conjunctivitis, C felis and FHV-1 were detected in 14 of 70 (20%) and in 23 of 70 (33%) animals, respectively. None of the 35 control cats were positive for C felis, whereas 7 (20%) of these cats were positive for FHV-1. Mixed infections were present in 5 of 70 cats (7%). Cats positive for C felis were significantly younger than control animals (P = .02), whereas no significant age differences were observed between FHV-1-positive cats and control cats (P = .41) or between FHV-1-positive animals and C felis-positive animals (P = .16). Cats sampled during acute-phase conjunctivitis were also investigated for the presence of C felis by conjunctival scrapings. In this acute phase, substantial agreement was found when comparing the results of the 2 methods (K = .80). The association between PCR results and conjunctivitis was evaluated for the 2 pathogens. The presence of C felis was significantly associated with conjunctivitis (P = .004), whereas the detection of FHV-1 did not significantly correlate with the clinical sign (P = .25), suggesting that, by itself. PCR is not suitable for the diagnosis of FHV-1-related conjunctivitis.

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Persistence of Herpes Simplex Virus Type 1 DNA in Chronic Conjunctival and Eyelid Lesions of Mice

Cited by 44 publications

References 34 publications

Persistence and Reactivation of Bovine Herpesvirus 1 in the Tonsils of Latently Infected Calves

Persistence and Reactivation of Bovine Herpesvirus 1 in the Tonsils of Latently Infected Calves

Herpes simplex virus 1 (HSV-1) DNA and immune complex (HSV-1–human IgG) elicit vigorous interleukin 6 release from infected corneal cells via Toll-like receptors

Prevalence of Chlamydophila felis and Feline Herpesvirus 1 in Cats with Conjunctivitis in Northern Italy

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