The Natural History of Recurrent Herpes Simplex Labialis

Spruance, Spotswood L.; Overall, James C.; Kern, Earl R.; Krueger, Gerald G.; Pliam, Victoria; Miller, William H.

doi:10.1056/nejm197707142970201

Cited by 312 publications

(141 citation statements)

References 23 publications

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“…ϩ T cell infiltration of the HSV-2-induced genital lesion precedes CD8 ϩ T cell infiltration and is associated, time-wise, with the drop in infectious virus titer (19,20).…”

Section: T Cells In Anti-hsv-2 Immunity Is As Producers Of Ifn-␥ (6)mentioning

confidence: 99%

Protective Immunity to Genital Herpes Simpex Virus Type 2 Infection Is Mediated by T-bet

Svensson

Nordström

Sun

et al. 2005

The Journal of Immunology

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We show, for the first time, that the transcription factor T-bet, which is implicated in IFN-γ production, is required for the induction of vaccine-induced antiviral immune protection. T-bet was found to be important in both the innate and acquired immune protection against genital HSV-2 infection. T-bet−/− and T-bet+/+ mice were infected vaginally with HSV-2 and examined daily for disease and mortality. T-bet−/− mice had significantly higher virus titers than T-bet+/+ mice following a primary HSV-2 infection, and succumbed significantly earlier to the infection. This result was associated with an impaired NK cell cytotoxic capacity and NK cell-mediated IFN-γ production in the T-bet−/− mice. To assess the induction of acquired antiviral immune protection, mice were vaccinated with an attenuated virus before infection. Vaccinated T-bet−/− mice could not control viral replication following an HSV-2 challenge and had significantly higher virus titers and mortality rates than vaccinated T-bet+/+ mice that remained healthy. The impaired acquired immune protection in T-bet−/− mice was associated with a significantly decreased HSV-2-specific delayed-type hypersensitivity response and a significantly reduced HSV-2-specific IFN-γ production from CD4+ T cells. However, T-bet deficiency did not impair either the IFN-γ production or the cytotoxic capacity of HSV-2-specific CD8+ T cells. We conclude that T-bet plays a crucial role in both the innate defense and the generation of vaccine-induced immunity against genital HSV-2 infection in mice.

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“…ϩ T cell infiltration of the HSV-2-induced genital lesion precedes CD8 ϩ T cell infiltration and is associated, time-wise, with the drop in infectious virus titer (19,20).…”

Section: T Cells In Anti-hsv-2 Immunity Is As Producers Of Ifn-␥ (6)mentioning

confidence: 99%

Protective Immunity to Genital Herpes Simpex Virus Type 2 Infection Is Mediated by T-bet

Svensson

Nordström

Sun

et al. 2005

The Journal of Immunology

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“…Although most primary infections are asymptomatic, HSV-1 and HSV-2 have a dynamic relationship with the human host, and transmission to other susceptible individuals is ensured by frequent episodes of reactivation; these episodes are also usually asymptomatic but release infectious virus into oral and genital tract secretions. Notably, the many hundreds of HSV reactivations from latency that occur in sensory ganglia over the lifetime of the infected individual seldom result in ganglionitis, peripheral neuropathy, or spread to the central nervous system (2)(3)(4).…”

mentioning

confidence: 99%

Herpes Simplex Virus 1 Tropism for Human Sensory Ganglion Neurons in the Severe Combined Immunodeficiency Mouse Model of Neuropathogenesis

Zerboni

Che

Reichelt

et al. 2013

J Virol

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bThe tropism of herpes simplex virus (HSV-1) for human sensory neurons infected in vivo was examined using dorsal root ganglion (DRG) xenografts maintained in mice with severe combined immunodeficiency (SCID). In contrast to the HSV-1 lytic infectious cycle in vitro, replication of the HSV-1 F strain was restricted in human DRG neurons despite the absence of adaptive immune responses in SCID mice, allowing the establishment of neuronal latency. At 12 days after DRG inoculation, 26.2% of human neurons expressed HSV-1 protein and 13.1% expressed latency-associated transcripts (LAT). Some infected neurons showed cytopathic changes, but HSV-1, unlike varicella-zoster virus (VZV), only rarely infected satellite cells and did not induce fusion of neuronal and satellite cell plasma membranes. Cell-free enveloped HSV-1 virions were observed, indicating productive infection. A recombinant HSV-1-expressing luciferase exhibited less virulence than HSV-1 F in the SCID mouse host, enabling analysis of infection in human DRG xenografts for a 61-day interval. At 12 days after inoculation, 4.2% of neurons expressed HSV-1 proteins; frequencies increased to 32.1% at 33 days but declined to 20.8% by 61 days. Frequencies of LAT-positive neurons were 1.2% at 12 days and increased to 40.2% at 33 days. LAT expression remained at 37% at 61 days, in contrast to the decline in neurons expressing viral proteins. These observations show that the progression of HSV-1 infection is highly restricted in human DRG, and HSV-1 genome silencing occurs in human neurons infected in vivo as a consequence of virus-host cell interactions and does not require adaptive immune control.T he simplex viruses, herpes simplex virus types 1 and 2 (HSV-1 and -2), are ubiquitous human viral pathogens that may cause mild to severe mucocutaneous infections (1). In rare instances, these viruses cause meningoencephalitis. The prevalence of HSV-1 infection among adults ranges from 50 to 90%. Primary HSV infection is acquired by inoculation of mucosal epithelium and abraded skin. Local replication facilitates retrograde axonal transport of HSV virions within innervating cutaneous sensory nerve fibers to the corresponding neuronal cell bodies in the peripheral dorsal root ganglia (DRG) or trigeminal ganglia, where latency is established. Although most primary infections are asymptomatic, HSV-1 and HSV-2 have a dynamic relationship with the human host, and transmission to other susceptible individuals is ensured by frequent episodes of reactivation; these episodes are also usually asymptomatic but release infectious virus into oral and genital tract secretions. Notably, the many hundreds of HSV reactivations from latency that occur in sensory ganglia over the lifetime of the infected individual seldom result in ganglionitis, peripheral neuropathy, or spread to the central nervous system (2-4).Lytic HSV-1 infection, which produces infectious progeny virions, involves transcription of more than 80 viral genes in a highly ordered process governed by sequential derepression ...

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“…In contrast to primary HSV-1, recurrent HSV-1 is rarely associated with systemic signs or symptoms except for local lymphadenopathy. The majority of patients are aware of prodromal symptoms that herald the onset of a reactivation episode, such as pain, burning, tingling, and pruritus [2]. These symptoms may last from 6 to 53 h prior to the appearance of the first vesicles [2].…”

mentioning

confidence: 99%

“…The majority of patients are aware of prodromal symptoms that herald the onset of a reactivation episode, such as pain, burning, tingling, and pruritus [2]. These symptoms may last from 6 to 53 h prior to the appearance of the first vesicles [2]. Recurrence patterns can demonstrate great variability from person to person.…”

mentioning

confidence: 99%