Herpes Simplex Virus Type 2 in the United States, 1976 to 1994

Fleming, Douglas T.; McQuillan, Geraldine M.; Johnson, Robert E.; Nahmias, André J.; Aral, Sevgi O.; Lee, F K; Louis, Michael E. St.

doi:10.1056/nejm199710163371601

Cited by 1,078 publications

(420 citation statements)

References 36 publications

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“…The epidemic of genital herpes continues to increase in the U.S.; ϳ22% of adults are infected with HSV-2, representing a 31% increase over the last decade (1). After primary infection at mucosal sites, HSV-2 remains latent in neuronal cells with intermittent HSV reactivations, resulting in the production of infectious virus with or without the onset of discernible disease.…”

mentioning

confidence: 99%

Long Term Persistence of Herpes Simplex Virus-Specific CD8+ CTL in Persons with Frequently Recurring Genital Herpes

Posavad

Huang²,

Barcy³

et al. 2000

The Journal of Immunology

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Herpes simplex virus (HSV) establishes a lifelong infection in humans. Reactivation of latent virus occurs intermittently so that the immune system is frequently exposed to viral Ag, providing an opportunity to evaluate memory T cells to a persistent human pathogen. We studied the persistence of genital herpes lesion-derived HSV-specific CD8+ CTL from three immunocompetent individuals with frequently recurring genital HSV-2 infection. All CTL clones were HSV-2 type specific and only one to three unique clonotypes were identified from any single biopsy specimen. The TCRBV genes utilized by these clonotypes were sequenced, and clonotype-specific probes were used to longitudinally track these clonotypes in PBMC and genital lesions. CTL clonotypes were consistently detected in PBMC and lesions for at least 2 and up to 7 years, and identical clonotypes infiltrated herpes lesions spaced as long as 7.5 years apart. Moreover, these clones were functionally lytic in vivo over these time periods. Additionally, CTL clones killed target cells infected with autologous viral isolates obtained 6.5 years after CTL clones were established, suggesting that selective pressure by these CTL did not result in the mutation of CTL epitopes. Thus, HSV recurs in the face of persistent CD8+ CTL with no evidence of clonal exhaustion or mutation of CTL epitopes as mechanisms of viral persistence.

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mentioning

confidence: 99%

Long Term Persistence of Herpes Simplex Virus-Specific CD8+ CTL in Persons with Frequently Recurring Genital Herpes

Posavad

Huang²,

Barcy³

et al. 2000

The Journal of Immunology

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“…The incidence of genital herpes infections caused by HSV-1 and 2 has increased significantly in the past 20 years (Fleming et al, 1997). Since the introduction of antiviral drugs in the early 1980s (Balfour, 1999), the management of genital herpes infections has improved considerably although it is not yet possible to cure herpes virus infections.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of amino acid ester prodrugs of acyclovir after oral administration: Interaction with the transporters on Caco-2 cells

Suresh¹,

Jain²,

Kwatra³

et al. 2008

International Journal of Pharmaceutics

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In vivo systemic absorption of the amino acid prodrugs of acyclovir (ACV) after oral administration was evaluated in rats. Stability of the prodrugs, L-Alanine-ACV (AACV), L-Serine-ACV (SACV), L-Isoleucine-ACV (IACV), γ-Glutamate-ACV (EACV) and L-Valine-ACV (VACV) was evaluated in various tissues. Interaction of these prodrugs with the transporters on Caco-2 cells was studied.In vivo systemic bioavailability of these prodrugs upon oral administration was evaluated in jugular vein cannulated rats. The amino acid ester prodrugs showed affinity towards various amino acid transporters as well as the peptide transporter on the Caco-2 cells. In terms of stability, EACV was most enzymatically stable compared to other prodrugs especially in liver homogenate. In oral absorption studies, ACV and AACV showed high terminal elimination rate constants (λ z ). SACV and VACV exhibited approximately five fold increase in area under the curve (AUC) values relative to ACV (p<0.05). C max(T) (maximum concentration) of SACV was observed to be 39 ± 22 µM in plasma which is 2 times better than VACV and 15 times better than ACV. C last(T) (concentration at the last time point) of SACV was observed to be 0.18 ± 0.06 µM in plasma which is 2 times better than VACV and 3 times better than ACV. Amino acid ester prodrugs of ACV were absorbed at varying amounts (C max ) and eliminated at varying rates (λ z ) thereby leading to varying extents (AUC). The amino acid ester prodrug SACV owing to its enhanced stability, higher AUC and better concentration at last time point seems to be a promising candidate for the oral treatment of herpes infections.

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“…6,7 HSV infection at birth may result from in utero exposure or may present later in the neonatal period as a result of perinatal or postnatal exposure. 1 It was previously demonstrated that for HSV infection acquired around the time of birth, the risk of neonatal HSV depends upon: (1) the viral load to which the infant is exposed, regardless of whether the mother has genital lesions with active shedding of HSV or is shedding asymptomatically; (2) maternal HSV infection/immunity status; 1,8,9 and (3) laceration of neonate's skin at the time of delivery by using an invasive technique such as scalp electrode and/or vacuum extraction for assisted delivery.…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus Infection after Vacuum-assisted Vaginally Delivered Infants of Asymptomatic Mothers

et al. 2004

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Herpes Simplex Virus Type 2 in the United States, 1976 to 1994

Cited by 1,078 publications

References 36 publications

Long Term Persistence of Herpes Simplex Virus-Specific CD8+ CTL in Persons with Frequently Recurring Genital Herpes

Long Term Persistence of Herpes Simplex Virus-Specific CD8+ CTL in Persons with Frequently Recurring Genital Herpes

Pharmacokinetics of amino acid ester prodrugs of acyclovir after oral administration: Interaction with the transporters on Caco-2 cells

Herpes Simplex Virus Infection after Vacuum-assisted Vaginally Delivered Infants of Asymptomatic Mothers

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