Experimental infection of Tupaia belangeri (tree shrews) with herpes simplex virus types 1 and 2.

The susceptibility of Tupaia belangeri (tree shrews, which are primitive prosimian primates) to infection with herpes simplex virus (HSV) and the pathogenesis of HSV in these animals were investigated. Juvenile (28--45 days old) and adult (150 days old) animals were inoculated intravenously, intraperitoneally, or subcutaneously with HSV type 1 or 2 (25--10(5) plaque-forming units per animal). Clinical illness usually appeared in juvenile animals on the second day after inoculation, and the animals died between two and 14 days after inoculation. High titers of infectious HSV were recovered from liver and spleen. The histopathologic examination always showed severe liver changes with numerous necrotic areas. The morphologic events in the liver were designated as herpetic hepatitis. The next most common morphologic findings were encephalitis and fibrosis in the spleen. These results demonstrate the high pathogenicity of HSV types 1 and 2 in juvenile T. belangeri. In contrast, adult animals did not develop acute clinical disease and survived the HSV infection.     

Age-specific prevalence of infection with herpes simplex virus types 2 and 1: a global review

Information on age- and sex-specific prevalence of herpes simplex virus (HSV) types 2 and 1 infections is essential to optimize genital herpes control strategies, which increase in importance because accumulating data indicate that HSV-2 infection may increase acquisition and transmission of human immunodeficiency virus. This review summarizes data from peer-reviewed publications of type-specific HSV seroepidemiologic surveys. HSV-2 prevalence is, in general, highest in Africa and the Americas, lower in western and southern Europe than in northern Europe and North America, and lowest in Asia. HSV-2 and -1 prevalence, overall and by age, varies markedly by country, region within country, and population subgroup. Age-specific HSV-2 prevalence is usually higher in women than men and in populations with higher risk sexual behavior. HSV-2 prevalence has increased in the United States but national data from other countries are unavailable. HSV-1 infection is acquired during childhood and adolescence and is markedly more widespread than HSV-2 infection. Further studies are needed in many geographic areas.     

Clinical and serologic features of herpes simplex virus infection in patients with AIDS.

We studied the natural history of herpes simplex virus (HSV) infection and its association with specific serum antibody in a sample of 68 HIV-infected patients with a first episode of Pneumocystis carinii pneumonia at San Francisco General Hospital in 1986. Seroprevalence was 66 and 77% for HSV-1 and HSV-2 antibody, respectively, by immunoblot assay. Twenty-seven patients had 45 HSV outbreaks diagnosed during 739 patient-months of follow-up. Median frequency of recurrence resulting in a medical visit was once every 6.5 months, and median duration of treated outbreak was 10 days. Fourteen of 48 evaluable patients seropositive for HSV-2 had no outbreak of HSV during a median follow-up of 7.5 months. Our data suggests that neither frequency nor severity of HSV were substantially increased in this group of patients, despite severe immunosuppression caused by HIV. However, validation of these results by a prospective study is required.     

Inability of enzyme immunoassays to discriminate between infections with herpes simplex virus types 1 and 2.

OBJECTIVE: To determine the accuracy of three commercial enzyme immunoassays in detecting and subtyping antibodies to herpes simplex virus type 1 or 2. DESIGN: Cross-sectional. SETTING: Referral medical center. PATIENTS: Ninety patients with culture-positive lesions caused by infection with herpes simplex virus type 1 or 2. The results of Western blot and glycoprotein G immunodot enzyme assays showed that an additional 53 patients had subclinical herpes simplex virus 2 infection, that another 20 patients had subclinical herpes simplex virus type 1 infection, and that 23 patients were seronegative. MEASUREMENTS: Three commercial enzyme immunoassays were used to determine herpes simplex virus antibody subtypes. MAIN RESULTS: All three commercial assays performed poorly in all patient groups (except in patients who were seronegative for herpes simplex virus). Among the 40 patients with a first episode of genital herpes, seroconversion to the appropriate viral type was shown by the three assays in only 33%, 55%, and 75% of cases. Among patients with recurrent genital herpes, the three commercial assays identified more than 90% of patients with only herpes simplex virus type 2 antibodies but failed to identify herpes simplex virus type 2 infections in 58% to 76% of patients with antibodies to both virus subtypes. The three assays correctly identified only 55%, 75%, and 85% of the 53 "silent carriers" of herpes simplex virus type 2. Overall, the three enzyme immunoassays detected herpes simplex virus type 2 antibodies in 60%, 62%, and 93% of patients with subtype 2 infections and falsely detected type 2 antibodies in 8%, 27%, and 49% of patients with type 1 infections. CONCLUSION: Currently licensed enzyme immunoassays give inaccurate or misleading results about the correct herpes simplex virus infecting subtype.     

Activation of an endogenous mouse type C virus by ultraviolet-irradiated herpes simplex virus types 1 and 2.

Infection of BALB/c mouse cells with UV-irradiated herpes simplex virus (HSV) types 1 and 2 resulted in activation of a xenotropic type C virus detected by infectious center formation in permissive rat cells. The levels of type C virus activated by HSV were related to the UV dose and the multiplicity of infection used. The ability of HSV to activate type C virus was eliminated by heat-inactivation and by neutralization with specific antiserum against HSV, but was not affected by purification or treatment with DNase and RNase. Maximum levels of type C virus in the cells and medium were observed within 1 day after HSV infection, and the levels returned to control cell values within 3-4 days. The possible significance of these findings with respect to the putative oncogenic potential of HSV is discussed.     

Neonatal herpes simplex virus infection

PURPOSE OF REVIEW: In spite of the availability of antiviral therapy for the treatment of neonatal herpes simplex virus infections, the outcome remains poor, particularly for babies with disseminated multi-organ infection or central nervous system disease. This review considers recent advances that impact on disease management. RECENT FINDINGS: Two areas of investigation have impacted on our understanding of neonatal herpes simplex virus infection. First, the transmission of infection from mother to baby has been clarified by extensive epidemiological investigations of genital herpes in pregnant women at term. Risk factors for neonatal herpes simplex virus disease include first-episode maternal infection in the third trimester, invasive monitoring, delivery before 38 weeks, and maternal age of less than 21 years. Regarding the management of neonatal herpes simplex virus disease, the utilization of high-dose acyclovir (20 mg/kg every 8 h) for 21 days significantly reduces mortality for babies with either encephalitis or disseminated disease. SUMMARY: Recent findings from epidemiological studies have identified women at risk of delivering a child who develops neonatal herpes simplex virus infection, and suggest methods to decrease maternal-fetal transmission. If infection is identified in the pregnant woman, cesarean delivery decreases the frequency of neonatal disease. With neonatal disease, acyclovir should be administered promptly at higher dosages and for longer periods than previously reported.     

Differential action of deoxynucleosides on mammalian cell cultures infected with herpes simplex virus types 1 and 2.

Cytopathic effects induced by eight serologically defined isolates of herpes simplex virus type 2 (tested on human amnion cells) were markedly inhibited by thymidine at a concentration of 5 mM; eight serologically defined isolates of herpes simplex virus type 1, however, were not significantly inhibited. A similar effect was seen with thymidine, deoxyguanosine, and deoxycytidine at 1-mM concentrations in tests with rabbit kidney cultures. The inhibitory effect of thymidine was not blocked by the simultaneous presence of deoxycytidine, which has been shown by others to release mammalian cells from thymidine suppression. Differential suppression of herpes simplex cytopathic effects by these deoxynucleosides provides further evidence of biochemical differences between herpes simplex types 1 and 2. This phenomenon offers a basis for rapid differentiation of type 1 from type 2.     

Expression of herpes simplex virus 1 glycoprotein B by a recombinant vaccinia virus and protection of mice against lethal herpes simplex virus 1 infection.

The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modified at the 5' end by in vitro oligonucleotide-directed mutagenesis. The modified gB gene was inserted into the vaccinia virus genome and expressed under the control of a vaccinia virus promoter. The mature gB glycoprotein produced by the vaccinia virus recombinant was glycosylated, was expressed at the cell surface, and was indistinguishable from authentic HSV-1 gB in terms of electrophoretic mobility. Mice immunized intradermally with the recombinant vaccinia virus produced gB-specific neutralizing antibodies and were resistant to a lethal HSV-1 challenge.     

Effect of immunization on acute and latent infections of vaginouterine tissue with herpes simplex virus types 1 and 2.

Inoculation of mice with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) by the vaginal route resulted in viral shedding during the acute phase of the infection and the development of a latent infection in vaginouterine tissue lasting up to one year in greater than 25% of the animals. Immunization with either serotype of HSV markedly reduced viral shedding when animals were subsequently challenged with the homologous serotype, but immunization with HSV-2 was significantly less effective in preventing the development of a latent infection in the vaginouterine tissue after challenge than was immunization with HSV-1.     

Herpes simplex virus type 2 and acute aseptic meningitis. Clinical features of cases with isolation of herpes simplex virus from cerebrospinal fluids.

Herpes simplex virus (HSV) was recovered from the cerebrospinal fluids (CSF) of 10 patients with acute aseptic meningitis. HSV type 1 was isolated from the CSF of a 6-month-old boy. The other 9 HSV isolates from CSF were from adults in the age-group 15 to 29 years; 7 of these isolates were available for typing and were identified as HSV type 2. In a further 9 patients with acute aseptic meningitis and belonging to the same age-group a HSV infection was suggested by a significant titre rise in complement-fixing antibodies against HSV. The clinical features of the 10 patients with HSV isolation from CSF are presented. The 6-month-old boy with HSV type 1 had an acute benign aseptic meningitis. Seven of the 9 adults with HSV isolation from CSF (type 2 in all isolates available for typing) had an acute uncomplicated aseptic meningitis, one patient (with type 2 isolated) had an acute meningoencephalitis and one (isolate untyped) an acute meningomyelitis.     

Ability of herpes simplex virus (HSV) types 1 and 2 to induce clinical disease and establish latency following previous genital infection with the heterologous HSV type

Guinea pigs were infected intravaginally with either herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2). One month postinoculation, animals were inoculated with the heterologous HSV type and observed for clinical disease and shedding of virus. One month after superinfection, animals were killed, and tissues were cocultivated to detect latent virus. Although the severity of clinical disease and the degree of shedding of virus were greatly reduced by prior infection with the heterologous virus type, superinfection did occur in 82%-90% of animals. Nervous system latency with the superinfecting virus was established in 20% of animals superinfected with HSV-2 and 55% superinfected with HSV-1. Of 21 animals tested, 5 had latent infection with both viruses, 6 with the superinfecting virus only, and 6 with the initial virus only. Protection from nervous system latency with the superinfecting virus correlated best with levels of serum neutralizing HSV antibody before superinfection.     

Chronic herpes simplex virus type-2 infection and HIV viral load

By December 2003, the estimated adult HIV/AIDS prevalence rate in sub-Saharan Africa was 7.5-8.5%, and rates of herpes simplex virus type-2 (HSV-2) infection among adults aged >30 years ranged from 60% to 82%. However, little is known about the natural history of HIV/HSV-2 co-infection in this population. We evaluated HIV viral load and CD4+ cell counts among persons with and without chronic HSV-2 co-infection in a cross-sectional study of HIV-infected persons not receiving antiretroviral therapy. HSV-2 and HIV co-infection was associated with a 0.3 log copies/mL higher HIV viral load compared with persons without HSV-2 infection (P=0.014). Chronic HSV-2 infection may have a negative effect on the clinical course of persons with HIV.