New concepts in understanding genital herpes

Abstract

Herpes Simplex Virus-2 (HSV-2) is a lifelong infection that causes recurrent genital ulcers and on rare occasions, disseminated and visceral disease. Herpes simplex virus-1 (HSV-1) infection is an increasingly important cause of genital ulcers as well. Herpes simplex virus (HSV) infections are the most common cause of genital ulcers in adults but acquisition and chronic infection are more commonly asymptomatic than symptomatic. Both the symptomatic and asymptomatic forms of HSV are of clinical consequence for several reasons. HSV-2 infection enhances HIV-1 acquisition, as well as transmission. In addition, both sexual and perinatal transmission can occur during asymptomatic viral shedding. Perinatal transmission is of particular concern because neonatal HSV infection results in severe morbiditiy to the newborn. Antiviral medicines are effective for limiting recurrence duration and decreasing transmission likelihood, though no available intervention completely prevents transmission. This highlights the importance of laboratory diagnostics for this lifelong infection, as well as the need for an HSV vaccine.Herpes simplex virus-2 (HSV-2) is the most common cause of genital ulcers, but can replicate in all human tissue and occasionally causes keratitis, hepatitis, pneumonitis, meningitis and neonatal sepsis. Seroprevalence is high worldwide and is 17% in the United States [1]. Though the predominant feature of HSV-2 infection is crops of painful lesions, most seropositive patients are asymptomatic and unaware of their diagnosis [2,3]. In symptomatic and asymptomatic persons, infection is characterized by frequent asymptomatic genital tract shedding [3][4][5], which promotes transmission [6], and persistent inflammation [7]. Immune cell infiltration may explain enhanced human immunodeficiency virus-1 (HIV-1) acquisition [8] and HIV-1 transmission [9] in HSV-2 infected persons. Short courses of DNA nucleoside analogues limit duration of primary infection [10] and recurrences [11], and prevent 50% of transmissions within discordant couples [12]. Because condoms [13,14] and education are only partially effective in preventing transmission, an HSV-2 vaccine is a public health priority. EpidemiologyHSV-2 infection is widely dispersed among populations worldwide [15]. HSV-2 is usually spread via sexual contact and appearance of HSV-2 antibodies in a population correlates with initiation of sexual activity during puberty. HSV-1 is an increasingly important cause of genital ulcer disease in the developed world [1,16]. In much of Asia and Africa, the majority of adults have HSV-1 antibodies and infection is typically acquired during childhood. Since World War II, childhood HSV-1 acquisition has decreased during childhood in certain Western populations. A recent consequence is an upsurge in sexually acquired HSV-1 infections in

Patient-Specific Neutralizing Antibody Responses to Herpes Simplex Virus Are Attributed to Epitopes on gD, gB, or Both and Can Be Type Specific

“…Second, a subunit vaccine should include both serotypes of gB and gD. It is worth noting that an ever increasing number of genital HSV infections are linked to HSV-1 (62). In the recent HSV-2 vaccine trial by GSK, this was certainly the case (7).…”

Repertoire of Epitopes Recognized by Serum IgG from Humans Vaccinated with Herpes Simplex Virus 2 Glycoprotein D

“…Within this age group, women are almost twice as likely to be affected as men (21.7% versus 11.3% seropositive, respectively) (1). Importantly, recent data suggest that in North America and Europe, HSV-1 is becoming an increasingly common cause of newly acquired genital herpes infections and now is more common than HSV-2 (2). Primary infection of the genital epithelium with HSV leads to lifelong latent infection of neurons of the sacral ganglia.…”

“…Reactivation and associated virus shedding may be accompanied by symptoms such as pain and ulceration at the site of virus replication. However, reactivation events frequently occur asymptomatically and may thus allow spread of virus without the knowledge of the infected individual (2,3). Several studies have also provided evidence that prior genital herpes infection increases the risk of acquiring sexually transmitted HIV (4,5).…”

Targeted DNA Mutagenesis for the Cure of Chronic Viral Infections

“…HSV-2 is the leading cause of genital ulcers worldwide, and 16% of Americans are seropositive (208). HSV-1 prevalence exceeds 50% in the United States: this serotype can cause both oral and genital ulceration and is the most common etiology of infectious blindness (keratitis) and viral encephalitis (158). Both varieties of HSV cause severe infections in newborns and immunocompromised hosts (17).…”