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An 8-month-old common marmoset (Callithrix jacchus) was presented with tic-like symptoms, and a 2-year-old pigmy marmoset (Callithrix pygmaea) was presented with dyspnea and hypersalivation. Both monkeys died within a few days, and necropsies were performed. Histopathological examinations revealed ulcerative stomatitis with epithelial cell swelling and eosinophilic intranuclear inclusion bodies in the oral epithelium of both cases. In the central and peripheral nervous systems, neuronal cell degeneration with intranuclear inclusion bodies was observed. Immunohistochemical examination using anti-herpes simplex virus type 1 antibody revealed virus antigens in both cases. Both animals had been kept as pets with limited exposure to the ambient environment except via their owners. Therefore, herpes simplex virus type-1 was probably acquired from close contact with their owners.

Herpes simplex virus 1 (HSV-1) causes a chronic, lifelong infection in >60% of adults. Multiple recent vaccine trials have failed, with viral diversity likely contributing to these failures. To understand HSV-1 diversity better, we comprehensively compared 20 newly sequenced viral genomes from China, Japan, Kenya, and South Korea with six previously sequenced genomes from the United States, Europe, and Japan. In this diverse collection of passaged strains, we found that one-fifth of the newly sequenced members share a gene deletion and one-third exhibit homopolymeric frameshift mutations (HFMs). Individual strains exhibit genotypic and potential phenotypic variation via HFMs, deletions, short sequence repeats, and single-nucleotide polymorphisms, although the protein sequence identity between strains exceeds 90% on average. In the first genome-scale analysis of positive selection in HSV-1, we found signs of selection in specific proteins and residues, including the fusion protein glycoprotein H. We also confirmed previous results suggesting that recombination has occurred with high frequency throughout the HSV-1 genome. Despite this, the HSV-1 strains analyzed clustered by geographic origin during whole-genome distance analysis. These data shed light on likely routes of HSV-1 adaptation to changing environments and will aid in the selection of vaccine antigens that are invariant worldwide.

Thelifelong latent infection-reactivation mode of infection of herpes simplex virus type 1 (HSV-1) transmitted by close contact has allowed a diversity of restriction fragment length polymorphism (RFLP) variations to accumulate in human populations. Whether and how the variants of the HSV-1 that is ubiquitous worldwide spread to different human populations is not clear. In our previous study the geographically gradient distribution of the HSV-1 BgK(L) variant, which is a good marker for the BgK(L):SaCFJ(M):SaGH(M):SaD/E(L):KpM(S) variant, suggested that BgK(L) dispersed geographically. Southern hybridization analyses showed that in BgK(L) the BglII cleavage site between the BglII K and small "Q/#13" fragments is lost, the SalI cleavage sites between the SalI J and C and between SalI F and J fragments are lost, and the SalI E fragment is abnormally large (SaE(L) variation). The RFLP and geographic distribution of one more HSV-1 RFLP variant, BgO(L), were comparatively analyzed. The BglII cleavage site between the BglII O and Q/#13 fragments is lost in BgOL. BgO(L) clinical isolates were not associated with any of the SaCFJ(M), SaE(L), SaGH(M), or KpM(S) variations, whereas one-fourth of the non-BgO(L):non-BgK(L) isolates was associated with SaCFJ(M) and SaGH(M), indicating that BgK(L) and BgO(L) are distant in terms of diversification. BgO(L) is distributed highly in the northeastern region and the southwestern island of Kyushu but is rare between the two regions in Japan, in a remarkable contrast to BgK(L). These are the first epidemiologic data to show contrasting geographic distribution profiles of two HSV-1 variants and suggest the gradual dispersion and replacement of HSV-1 variants.

Restriction endonuclease fragment length polymorphism (RFLP) is useful for the epidemiological study of herpes simplex virus type 1 (HSV-1). We report here the identification of a major BglII RFLP variant of HSV-1, designated BgKL, found in 27.0% of 636 HSV-1 clinical isolates. We have also established its geographic distribution in Japan. BgKL has an unusually large BglII K fragment. SalI cleavage analyses showed that 97% of BgKL variant isolates lack both the SalI C-J and the F-J cleavage sites and have an unusually large SalI D or E fragment, and 91% of the BgKL variants lack both SalI G and H fragments. Furthermore, 96% of BgKL isolates have an unusually small KpnI M fragment. Therefore, BgKL is a marker for these five mutations in most HSV-1 isolates and is a useful HSV-1 RFLP marker. The BgKL variant was found in 59% of HSV-1 isolates from Shikoku Island, 44% of HSV-1 isolates from the Chugoku region of Honshu Island, 31% of HSV-1 isolates from Kyushu Island, 0% of HSV-1 isolates from Okinawa Island, 49% of HSV-1 isolates from Osaka, 27% of HSV-1 isolates from Shiga, 13% of HSV-1 isolates from the Chubu Region, and 9% of HSV-1 isolates from the Tohoku Region of Honshu Island. Differences in the frequency of BgKL between the Shikoku-Chugoku-Osaka area (49%) and Kyushu, between Kyushu and Okinawa, between the Shikoku-Chugoku-Osaka area and Shiga, and between Shiga and Tohoku are all statistically significant. The BgKL frequency decreases in a geographical gradient suggest that this HSV-1 variant was dispersed from Shikoku to the surrounding regions and then to more distant regions. The BgKL frequency in Tokyo was similar to the nationwide average. These are the first data to suggest a geographic and demographic dispersion pattern of HSV-1. Implications for the epidemiology and diversification of HSV-1 are discussed.

Comparisons of the seroepidemiology of genital herpes simplex virus (HSV) infection within and between countries are hampered by variations in tests, methods and populations sampled. Differences in seroprevalence may partly reflect variability in diagnostic efforts and healthcare awareness, expectations and utilization. To allow comparison between surveys and to improve their performance, seroepidemiological studies should use validated HSV type-specific tests, report age-specific or age-adjusted prevalence and define the period of time over which samples were collected. Despite the difficulty of comparing studies, the prevalence of HSV-2 infection varies between developed countries. Among healthy adult populations, HSV-2 seroprevalence is higher in the USA than in Europe. Furthermore, HSV-2 seroprevalence varies widely among European countries. For example, in 1989 HSV-2 seroprevalence among pregnant women was reported to be 33% in Sweden compared with 8.3% in Germany. In some, but not all, countries, HSV-2 seroprevalence appears to be increasing. In the USA, the National Health and Nutrition Examination Surveys found that HSV-2 seroprevalence increased by almost one third from 16.4% to 21.8% from 1976 to 1994 in people over 12 years old. The incidence of HSV infection is a measure of primary infection. HSV incidence is difficult to quantify, partly due to unrecognized or asymptomatic infections. However, estimates of incidence in North American and European populations range from 5 to 24 per 100 people per year. Prevention programmes should recognize that HSV-2 seroprevalence increases rapidly in early adult life. The proportion of genital herpes infections caused by HSV-1 is increasing in the developed world, possibly due to changes in oral-genital sexual behaviour and lower rates of HSV-1 acquisition in childhood.

Background/aims: It is reported by the national surveillance of ocular infectious diseases in Japan that 4.3% of cases of epidemic keratoconjunctivitis (EKC) diagnosed clinically were caused by herpes simplex virus (HSV). Clinical and virological studies of patients with HSV conjunctivitis were carried out., Methods: The study population consisted of 478 patients with acute follicular conjunctivitis. Virological analysis was carried out for adenovirus (Ad) and HSV by the cell culture method and fluorescein antibody (FA) method. Polymerase chain reaction for Chlamydia trachomatis was also carried out., Results: From 23 patients, HSV type 1 was isolated but Ad or C trachomatis was not isolated. 87% of cases were unilateral. Most cases showed clinical resolution within 9 days. Early corneal lesions and preauricular lymphadenopathy were less frequent in HSV conjunctivitis than in adenoviral conjunctivitis, especially that due to subgenus D. No case showed a positive result for HSV by the FA method using conjunctival swabs; however, the FA test was positive in all strains isolated by cell culture., Conclusions: These results indicate that it is difficult clinically to differentiate HSV conjunctivitis from adenoviral conjunctivitis in the acute stage, since the clinical features of adenoviral conjunctivitis are similar to those of HSV conjunctivitis. A biological difference may exist between HSV strains causing keratitis and conjunctivitis.

Purpose: To determine the type of herpes simplex virus in acute retinal necrosis syndrome associated with herpes simplex virus., Methods: Herpes simplex virus type 1, herpes simplex virus type 2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus were examined by polymerase chain reaction in intraocular specimens from 16 patients with acute retinal necrosis syndrome. Anti-herpes simplex virus type 1 and anti-herpes simplex virus type 2 type-specific antibodies in serum from the patients were detected by enzyme immunoassay., Results: Of 16 patients with acute retinal necrosis syndrome, seven were polymerase chain reaction positive for herpes simplex virus type 2 and nine were positive for varicella-zoster virus. Anti-herpes simplex virus type 2 antibody was positive and anti-herpes simplex virus type 1 antibody was negative in the sera of the seven patients with herpes simplex virus type 2 DNA-positive acute retinal necrosis syndrome. In contrast, anti-herpes simplex virus type 2 antibody was absent in all nine varicella-zoster virus DNA-positive acute retinal necrosis syndrome patients., Conclusion: Herpes simplex virus type 2 has been demonstrated to be the major causative agent in acute retinal necrosis syndrome associated with herpes simplex virus by molecular biological and serological methods. Negative preexisting anti-herpes simplex virus type 1 antibody may play an important role in acute retinal necrosis syndrome associated with herpes simplex virus type 2.

Recurrent acyclovir (ACV)-resistant (ACV-r) herpes simplex virus type 1 (HSV-1) infections occurred in a patient with Wiskott-Aldrich syndrome, an X-linked recessive immunodeficiency syndrome composed of three clinical characteristics of immunodeficiency, thrombocytopenia, and an eczematous dermatitis. The patient had severe and recurrent ACV-r herpes simplex and was treated with vidarabine in a satisfactory manner from 1993 to 1997. During the 4-year observation period, two ACV-sensitive (ACV-s) HSV-1 isolates and five ACV-r HSV-1 isolates were recovered. The nucleotide sequence of the thymidine kinase (TK) gene from these sequential ACV-r isolates was compared with the ACV-s isolates. A single nucleotide deletion of cytosine (C) from homopolymer stretch of four C residues between nucleotide 1061 and 1064 of the open reading frame was found in all ACV-r isolates. No other differences were observed in the TK nucleotide sequence between ACV-s and ACV-r isolates. The TK nucleotide sequences of the two ACV-s isolates were identical to each other and those of the five ACV-r isolates were identical to one another. These results suggest that the ACV-r HSV-1 might have derived from the ACV-s strain in the patient body and that TK-associated ACV-r HSV-1 can reactivate from latency.

Background: We set out to establish the epidemiology of viral conjunctivitis over a 10-year period in Sapporo, northern Japan., Methods: A total of 965 patients with clinically suspected viral conjunctivitis during the 10-year period from 1985 to 1994 in Sapporo were evaluated., Results: Among the 965 patients, cumulative frequency of adenovirus (Ad) was 721 (75%). The dominant serotype of Ad changed with time; each serotype peaked at 3- to 5-year intervals. Adenoviral conjunctivitis occurred most often in July and August each year. Ad3 and Ad4 were predominantly identified in patients 30-39 years old. No enterovirus 70 has been detected. Herpes simplex virus (HSV) and Chlamydia trachomatis had no significant peak. HSV was isolated throughout the year, and C. trachomatis had two peaks of detection: in March and from July to September. HSV and C. trachomatis were predominantly detected in patients 20-29 years old., Conclusion: In this study, the main etiological agent of viral conjunctivitis in Sapporo, Japan, was Ad; however, attention should be paid to non-adenoviral agents, such as HSV and C. trachomatis, as possible causes of acute conjunctivitis.