Microbial Diversity of Genital Ulcers of HSV-2 Seropositive Women.

We measured the microbial community structure of genital ulcers in women. Swabs from clinically detected ulcers were tested for HSV-2 and Treponema pallidum by polymerase chain reaction (PCR). HSV-2 and T. pallidum were detected by serum antibody testing. Microbial community structure was characterized by high-throughput 16 s rRNA gene amplicon sequencing. Multiple group testing and Elastic net and Lasso regressions identified taxa associated with differences in factors of interest. Among 49 ulcer specimens from 49 HSV-2 seropositive women, by PCR HSV-2 was recovered from 28 (57%) specimens and T. pallidum from none; one woman showed serologic evidence of syphilis. Overall, 63% of women were HIV-positive and 49% had an uncircumcised male sex partner. By both multiple group testing and regression, Porphyromonas (FDR p-value = 0.02), Prevotella (FDR p-value = 0.03), Anaerococcus (FDR p-value = 0.07), and Dialister (FDR p-value = 0.09) were detected at higher relative abundance in HSV-2 PCR-positive than negative ulcers. The presence of HSV-2 in a lesion was associated with presumed bacterial agents of Bacterial vaginosis. Differences in bacterial communities may contribute to HSV-2 ulcer pathogenesis, severity, or prolonged healing. If these results are confirmed, future studies may consider the influence of BV treatment on women's GUD and HSV-2 incidence and recurrence.

Pseudoepitheliomatous hyperplasia causing a painful plaque in a HIV-infected female.

Dermatological conditions are more common and can present atypically, in human immunodeficiency virus-infected individuals. This case report describes a 22-year-old human immunodeficiency virus-positive Caucasian female who presented with a vulval lesion eight weeks after starting antiretroviral treatment. Clinical examination revealed a 2 cm well-demarcated plaque on the outer aspect of the left labium minus. The lesion was tender, no contact bleeding or ulceration present. She was presumptively treated for chancroid and herpes simplex with 500 mg ceftriaxone IM stat, 1 g azithromycin PO stat, and valacyclovir 500 mg BD for five days. The lesion persisted despite treatment, and during follow-up, a punch biopsy was carried out. She was diagnosed with pseudoepitheliomatous hyperplasia of the epidermis. In addition to highlighting this condition that has been previously reported in human immunodeficiency virus/herpes simplex virus co-infection, this case demonstrates that unusual skin presentations must be considered in human immunodeficiency virus-infected individuals and illustrates the importance of biopsy for any non-healing lesions.

Distinct Effects of the Cervicovaginal Microbiota and Herpes Simplex Type 2 Infection on Female Genital Tract Immunology.

Background: Genital inflammation is a key determinant of human immunodeficiency virus (HIV) transmission, and may increase HIV-susceptible target cells and alter epithelial integrity. Several genital conditions that increase HIV risk are more prevalent in African, Caribbean, and other black (ACB) women, including bacterial vaginosis and herpes simplex virus type-2 (HSV-2) infection. Therefore, we assessed the impact of the genital microbiota on mucosal immunology in ACB women and microbiome-HSV-2 interactions. Methods: Cervicovaginal secretions and endocervical cells were collected by cytobrush and Instead Softcup, respectively. T cells and dendritic cells were assessed by flow cytometry, cytokines by multiplex enzyme-linked immunosorbent assay (ELISA), and the microbiota by 16S ribosomal ribonucleic acid gene sequencing. Results: The cervicovaginal microbiota of 51 participants were composed of community state types (CSTs) showing diversity (20/51; 39%) or predominated by Lactobacillus iners (22/51; 42%), L. crispatus (7/51; 14%), or L. gasseri (2/51; 4%). High-diversity CSTs and specific bacterial phyla (Gardnerella vaginalis and Prevotella bivia) were strongly associated with cervicovaginal inflammatory cytokines, but not with altered endocervical immune cells. However, cervical CD4+ T-cell number was associated with HSV-2 infection and a distinct cytokine profile. Conclusions: This suggests that the genital microbiota and HSV-2 infection may influence HIV susceptibility through independent biological mechanisms.

Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota.

Cervical human papillomavirus (HPV) infection may increase HIV risk. Since other genital infections enhance HIV susceptibility by inducing inflammation, we assessed the impact of HPV infection and clearance on genital immunology and the cervico-vaginal microbiome. Genital samples were collected from 65 women for HPV testing, immune studies and microbiota assessment; repeat HPV testing was performed after 6 months. All participants were HIV-uninfected and free of bacterial STIs. Cytobrush-derived T cell and dendritic cell subsets were assessed by multiparameter flow cytometry. Undiluted cervico-vaginal secretions were used to determine cytokine levels by multiplex ELISA, and to assess bacterial community composition and structure by 16S rRNA gene sequence analysis. Neither HPV infection nor clearance were associated with broad differences in cervical T cell subsets or cytokines, although HPV clearance was associated with increased Langerhans cells and HPV infection with elevated IP-10 and MIG. Individuals with HPV more frequently had a high diversity cervico-vaginal microbiome (community state type IV) and were less likely to have an L. gasseri predominant microbiome. In summary, HPV infection and/or subsequent clearance was not associated with inflammation or altered cervical T cell subsets, but associations with increased Langerhans cells and the composition of the vaginal microbiome warrant further exploration.

Chlamydial Pre-Infection Protects from Subsequent Herpes Simplex Virus-2 Challenge in a Murine Vaginal Super-Infection Model.

Chlamydia trachomatis and Herpes Simplex Virus-2 (HSV-2) genital tract co-infections have been reported in humans and studied in vitro but the clinical consequences are unknown. Limited epidemiologic evidence suggests that these co-infections could be more severe than single infections of either pathogen, but the host-pathogen interactions during co-infection remain uncharacterized. To determine whether disease progression and/or pathogen shedding differs between singly-infected and super-infected animals, we developed an in vivo super-infection model in which female BALB/c mice were vaginally infected with Chlamydia muridarum (Cm) followed later by HSV-2. Pre-infection with Chlamydia 3 or 9 days prior to HSV-2 super-infection conferred significant protection from HSV-2-induced neurologic disease and significantly reduced viral recovery compared to HSV-2 singly-infected controls. Neither protection from mortality nor reduced viral recovery were observed when mice were i) super-infected with HSV-2 on day 27 post Cm; ii) infected with UV-irradiated Cm and super-infected with HSV-2; or iii) azithromycin-treated prior to HSV-2 super-infection. Therefore, protection from HSV-2-induced disease requires active infection with viable chlamydiae and is not observed after chlamydial shedding ceases, either naturally or due to antibiotic treatment. Thus, Chlamydia-induced protection is transient and requires the continued presence of chlamydiae or their components. These data demonstrate that chlamydial pre-infection can alter progression of subsequent HSV-2 infection, with implications for HSV-2 transmission from co-infected humans.

[IS A NONBACTERIAL PROSTATITIS NONBACTERIAL?].

The study involved 287 patients with chronic recurrent urethroprostatitis. In 83 (28.9%) of them the bacterial microflora in prostatic secretions was detected. The remaining 204 patients with nonbacterial prostatitis underwent in-depth laboratory testing. Cytological and immunological methods, electron microscopy, PCR, McCoy cell culture and developed by the authors the pre-culture pathogen accumulation technique were used to investigate urethral and prostatic smears. As a result C. trachomatis was detected in 84.8% of patients, T. vaginalis--75.5%, and viruses of the Herpesviridae family--in 68.6%. Co-infection was diagnosed in 82.4% of patients, no infection was found in 6.9% of patients. The highest diagnostic sensitivity and specificity were observed in the pre-culture pathogen accumulation technique. According to electron microscopy, T. vaginalis was presented in several morphological shapes: flagellated, spherical and amoeboid. Thus, in 93.1% of patients who had previously been diagnosed with nonbacterial prostatitis by standard bacterial culture, the in-depth microbiological examination identified atypical infections (chlamydia, herpes virus, trichomonas), revealing that the rate of real nonbacterial (non-infectious) prostatitis did not exceed 6.9%.

CD18 deficiency evolving to megakaryocytic (M7) acute myeloid leukemia: case report.

Leukocyte adhesion deficiency type 1 (LAD 1 - CD18 deficiency) is a rare disease characterized by disturbance of phagocyte function associated with less severe cellular and humoral dysfunction. The main features are bacterial and fungal infections predominantly in the skin and mucosal surfaces, impaired wound healing and delayed umbilical cord separation. The infections are indolent, necrotic and recurrent. In contrast to the striking difficulties in defense against bacterial and fungal microorganisms, LAD 1 patients do not exhibit susceptibility to viral infections and neoplasias. The severity of clinical manifestations is directly related to the degree of CD18 deficiency. Here, a 20 year-old female presenting a partial CD18 deficiency that developed a megakaryocytic (M7) acute myeloid leukemia is described for the first time. The clinical features of the patient included relapsing oral thrush due to Candida, cutaneous infections and upper and lower respiratory tract infections, followed by a locally severe necrotic genital herpetic lesion. The patient's clinical features improved for a period of approximately two years, followed by severe bacterial infections. At that time, the investigation showed a megakaryocytic acute myeloid leukemia, treated with MEC without clinical improvement. The highly aggressive evolution of the leukemia in this patient suggests that adhesion molecules could be involved in the protection against the spread of neoplastic cells.

Vulvar pseudoepitheliomatous hyperplasia associated with herpes simplex virus type II mimicking cancer in an immunocompromised patient.

We report an exaggerated dermatological inflammatory condition in an immunocompromised patient. The patient was a 51-year-old woman who had HIV infection and a history of cervical cancer. Three years after highly active antiretroviral therapy with an improved immune status, and 2 years after remission of cervical cancer, she developed verrucous perineal masses. Provisional diagnosis was recurrent cervical cancer or primary vulvar cancer. Pathological features revealed pseudoepitheliomatous hyperplasia associated with herpes viral infection. After minimal response to systemic oral antiviral drugs and topical imiquimod, she had clinical resolution with the addition of systemic oral corticosteroid.

Optical coherence tomography for assessment of microbicide safety in a small animal model.

Sensitive imaging techniques for small animals are needed to assess drug toxicity in preclinical studies. Optical coherence tomography (OCT) provides a noninvasive tool for high-resolution, depth-resolved visualization of drug-induced changes in tissue morphology. In a mouse model, we utilize OCT to assess vaginal tissue integrity following the application of topical microbicides (drugs used to prevent infection). Mice are challenged with herpes simplex virus-2 (HSV-2) to determine the correlation of tissue damage as quantified by OCT to increased susceptibility. The microbicide benzalkonium chloride (BZK) (0.02, 0.2, or 2%) or phosphate buffered saline control is administered intravaginally. In vivo OCT imaging and collection of tissue samples are performed after treatment. A quantitative OCT scoring system is applied to assess epithelial damage, and the results are compared with those of histology. A separate group of mice are treated similarly then challenged with HSV-2. Epithelial morphology quantified noninvasively by OCT and histology are dose-dependent (p<0.0001). The OCT scoring system detected a significant increase in epithelial damage with increasing BZK concentration (p<0.0001). These results paralleled an increase in HSV-2 susceptibility (p<0.005). OCT can be used as a noninvasive tool to assess topical drug toxicity in a small animal model with potential to predict increased susceptibility to vaginal infection.

Recalcitrance of bacterial vaginosis among herpes-simplex-virus-type-2-seropositive women.

AIM: The multifactorial etiology of bacterial vaginosis (BV) impedes development of effective treatment and prevention strategies. Herein, we evaluated the effects of herpes simplex virus type 2 (HSV-2), a suspected BV risk factor, on vaginal flora composition. MATERIALS AND METHODS: Correlations between HSV-2 infection and BV were prospectively explored among 12 HSV-2-seropositive women with asymptomatic BV who were asked to collect daily vaginal swab specimens for Gram stain analysis of vaginal flora and determination of HSV-2 shedding frequencies during the 1month before and after metronidazole therapy. RESULTS: Unlike prior longitudinal studies that reported rapid fluctuations in vaginal flora composition and frequent episodes of spontaneously resolving BV, we found that 99.4% (310/312) of vaginal smears collected before initiation of metronidazole were consistent with a diagnosis of BV. Effectiveness of metronidazole therapy was also much lower than previously reported in studies not restricting enrollment to HSV-2-seropositive women; we observed a BV recurrence rate of 89% in the first month after completion of therapy while the median time to this recurrence occurred only 14days after treatment. CONCLUSIONS: Our study demonstrates BV recalcitrance among HSV-2-infected women and provides additional evidence for a linkage between this chronic viral infection and abnormal vaginal flora. Additional work will be needed to define mechanisms responsible for this correlation and to determine if vaginal flora health of HSV-2-infected women is improved by medications that suppress HSV-2 shedding.

[Comprehensive examination of the female urogenital tract infection by polymerase chain reaction using multiplex test systems].

The results of the polymerase chain reaction studies performed in 2006-2008 were used to make a retrospective analysis of the detection of urogenital herpesvirus infections in reproductive-aged women constituting the urban population of the central region of Russia. The study used both monotarget and mutiplex test systems to detect herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus types 6 and 7. A total of about 7.500 referrals; the detection rate for HSV was about 1%; that for CMV was from 0.3 in 2006 to 1% in 2008; that for EBV was from 0.1% in 2006 to 0.3% in 2008. More than a half of HSV-, CMV-, or EBY-positive samples also contained DNA of other causative agents and some samples did two pathogens or more. Multiplex test systems for herpesviruses considerably enhance the efficiency of diagnostic studies and reduce the material and time costs of diagnosis.

Risk factors for herpes simplex virus type 2 and its association with HIV among pregnant teenagers in Zimbabwe.

Herpes simplex virus type 2 (HSV-2) causes a chronic infection that is recognised as the leading cause of genital ulcer disease worldwide and is known to increase the risk of HIV infection. In a cross-sectional study we examined risk factors for HSV-2 among 176 pregnant teenagers recruited from three primary health care clinics in Zimbabwe. The prevalence of HSV-2 and HIV were 41.6% and 29.2% respectively. HIV-infected teenagers were more likely to be HSV-2 seropositive compared with the HIV uninfected teenagers, odds ratio (OR) 7.9 (95% confidence interval (CI) 3.7-16.9). In multivariate analysis having an older partner remained independently associated with HSV-2 seropositivity, OR 2.9 (95% CI 1.2-6.9) suggesting that risk factors for HSV-2 seropositivity among pregnant teenagers depend primarily on the behaviour of the male partners.

Herpes simplex virus type 2 and Chlamydia trachomatis in adenocarcinoma of the uterine cervix.

INTRODUCTION: Adenocarcinoma of the uterine cervix (AC) occurs in 15-20% of primary cervical neoplasias. Although some etiologic factors for squamous cell carcinoma are well defined, and its relationship with sexually transmitted disease as human papillomavirus (HPV) is established, we still do not know about the causative factors of most of AC besides HPV infection. OBJECTIVES: To determine the presence of herpes simplex virus type 2 (HSV-2) and Chlamydia trachomatis (CT) DNA in AC specimens, and its correlation with HPV infection. METHODS: 206 paraffin-embedded cases of AC were selected to DNA extraction. The specimens and the DNA were isolated. Samples were first screened for beta-globin DNA sequences, and 67 cases were considered adequate to further analysis. In a previous analysis, DNA of HPV was identified in 79.4% of specimens included in this series (51% HPV 18 and 34% HPV 16). The local ethical committee approved the study. RESULTS: All samples were negative for HSV-2 DNA and CT DNA. CONCLUSIONS: In our series HSV-2 DNA and CT DNA were not found to be integrated to the genome of adenocarcinoma of the uterine cervix and do not seem to be a co-factor for HPV on the etiology of this histologic subtype.

The microenvironment of vulvar skin in women with symptomatic and asymptomatic herpes simplex virus type 2 (HSV-2) infection.

BACKGROUND: It is not known why some individuals infected with herpes simplex virus type 2 (HSV-2), experience frequent recurrences, while most of those infected have a completely silent infection. OBJECTIVE: We wanted to study if local factors in the skin could explain this difference. DESIGn 21 HSV-2 seropositive patients, 10 with history of >8 clinical recurrences a year (symptomatics) and 11 without symptoms of genital herpes (asymptomatics) were included. All had to answer a questionnaire. With standardised methods, the skin temperature, pH, and the skin barrier function, expressed as transepidermal water loss (TEWL) and skin capacitance, were measured on labium majus and perineum. Culture for bacteria was performed from the same regions. RESULTS AND CONCLUSION: No significant differences in terms of pH and skin barrier function were registered between symptomatic and asymptomatic patients. Asymptomatic patients had a tendency (0.06) to a higher colonisation with lactobacilli on labium majus than symptomatic patients.

Poor correlation between genital lesions and detection of herpes simplex virus in women in labor.

OBJECTIVE: To estimate the accuracy of clinical diagnosis of genital herpes for herpes simplex virus (HSV) detection among women in labor. METHODS: Viral detection by culture and HSV DNA polymerase chain reaction (PCR) among women who underwent cesarean delivery for genital herpes was compared with women without HSV symptoms in labor who had genital swabs collected for HSV culture and to a subset of these women who had genital specimens available for PCR analysis, regardless of culture results. RESULTS: From 1989 to 1999, 126 of 19,568 (0.6%) women underwent cesarean delivery for HSV. Twenty-six percent of 110 of these women had HSV detected by culture from at least 1 genital specimen and 46% of 70 of these women had HSV detected by PCR. During the same period, 61 of 12,623 (0.5%) asymptomatic women had HSV detected by culture. Between 1995 and 1996, 57 of 2,109 (2.7%) asymptomatic women had HSV detected by PCR. Thus, the presence of genital lesions had a sensitivity for HSV detection of 37% by culture and 41% by PCR. The amount of HSV present in asymptomatic women with HSV detected in genital secretions by PCR was often as high as those with genital lesions, although the median amount of HSV DNA detected was greater in women with lesions. CONCLUSION: Clinical diagnosis of genital herpes at the time of labor correlates relatively poorly with HSV detection from genital sites or lesions by culture or PCR and fails to identify asymptomatic women who have HSV in their genital secretions at the time of labor.

Induction of secretory aspartyl proteinase of Candida albicans by HIV-1 but not HSV-2 or some other microorganisms associated with vaginal environment.

The most common type of candidiasis involves mucosal sites such as the oral cavity, the gastrointestinal tract and the vagina. Among many of virulence factors, the production of secretory aspartyl proteinase (Sap) by Candida albicans (C. albicans) has gained much attention, and factors leading to Sap induction are thus under intense study. The aim of this study was to examine whether some microorganisms such as Lactobacillus, Gardnerella vaginalis (G. vaginalis), human immunodeficiency virus type-1 (HIV-1) and human herpes simplex virus type-2 (HSV-2) had any Sap inducing effect on C. albicans. Here we showed that among the microorganisms tested in vitro only HIV-1 induced Sap production from C. albicans.

Sexually transmitted infections in men.

The diagnosis and treatment of STDs is a common problem in primary care practice; however, newer diagnostic and therapeutic alternatives require physicians to be aware of evidence-based guidelines that are continuing to evolve. The treatment of STDs in men, in particular, is an area of evolving evidence because much of what is known is based on the treatment of STDs in women. Men represent unique challenges in diagnosis, evaluation, and follow-up that need to be considered in the treatment of urethritis, epididymitis, herpes genitalis, condyloma, prostatitis, and other syndromes. Screening for asymptomatic STDs is currently not recommended in the general population, but selected criteria can be used to identify a target population for screening in high-risk areas.

A prospective study of new infections with herpes simplex virus type 1 and type 2. Chiron HSV Vaccine Study Group.

BACKGROUND AND METHODS: Herpes simplex virus (HSV) infections are endemic, but the clinical characteristics of newly acquired HSV type 1 (HSV-1) and HSV type 2 (HSV-2) infections in adults have not been rigorously defined. We monitored 2393 sexually active HSV-2-seronegative persons for clinical and serologic evidence of new HSV infection. Of the participants, 1508 were seropositive for HSV-1 and 885 were seronegative. Charts were reviewed in a blinded manner for classification of those with genitourinary or oropharyngeal symptoms. Charts were also reviewed for all 174 persons with HSV seroconversion. RESULTS: The rates of new HSV-1 and HSV-2 infections were 1.6 and 5.1 cases per 100 person-years, respectively. Of the 155 new HSV-2 infections, 57 (37 percent) were symptomatic, 47 of which (82 percent) were correctly diagnosed at presentation. Among the 74 patients given a clinical diagnosis of genital HSV-2 during the study, 60 were given a correct diagnosis and 14 were given an incorrect diagnosis of genital herpes, for a ratio of true positive results to false positive results of 4:1. Among the 98 persons with asymptomatic HSV-2 seroconversion, 15 percent had genital lesions at some time during follow-up. Women were more likely than men to acquire HSV-2 (P<0.01) and to have symptomatic infection. Previous HSV-1 infection did not reduce the rate of HSV-2 infection, but it did increase the likelihood of asymptomatic seroconversion, as compared with symptomatic seroconversion, by a factor of 2.6 (P<0.001). Of the 19 new HSV-1 infections, 12 were symptomatic. The rates of symptomatic genital HSV-1 infection and oropharyngeal HSV-1 infection were the same (0.5 case per 100 person-years). CONCLUSIONS: Nearly 40 percent of newly acquired HSV-2 infections and nearly two thirds of new HSV-1 infections are symptomatic. Among sexually active adults, new genital HSV-1 infections are as common as new oropharyngeal HSV-1 infections.

The association of herpes simplex virus type 2 (HSV-2), Haemophilus ducreyi, and syphilis with HIV infection in young men in northern Thailand.

To evaluate the association between sexually transmitted diseases that commonly may cause genital ulceration and prevalent and incident HIV infections, we conducted three case control studies in a cohort of 21-year-old male military conscripts in northern Thailand. The men were evaluated at baseline in 1991 and semiannually until their discharge 2 years later. Serologic evidence of infection with herpes simplex virus type 2 (HSV-2), Haemophilus ducreyi, and HIV were more frequent at baseline in 83 men with a history of genital ulcer than in 97 men without such a history. Seropositivity to H. ducreyi (odds ratio [OR] = 3.46), HSV-2 (OR = 3.83), and syphilis (OR = 1.53) were more common in HIV-positive than HIV-negative men. Men (N = 45) who seroconverted to HIV while in the military were more often seropositive for H. ducreyi and HSV-2 before HIV seroconversion and also were more likely to seroconvert to HSV-2 and H. ducreyi during the same interval as their HIV seroconversion compared with men who remained HIV-negative. These data suggest that HSV-2 and H. ducreyi may be both markers for high-risk sexual behavior and risk factors for HIV infection among young men in Thailand.

PIP: Three case-control studies conducted in 1991-93 in a cohort of 21-year-old male military conscripts in northern Thailand investigated the association between HIV infection and three sexually transmitted diseases (STDs) commonly associated with genital ulceration: herpes simplex virus type 2 (HSV-2), Haemophilus ducreyi, and Treponema pallidum. The studies compared 83 men with a history of genital ulcer disease (GUD) at baseline and 97 men without such a history, 103 men who were HIV-positive at baseline and 110 randomly selected HIV-negative conscripts, and 45 men who seroconverted to HIV while they were in the military and 124 men who remained HIV-negative throughout military service. The first study detected a significant dose-response association between number of commercial sex worker visits in the past year, lifetime number of sexual partners, and a history of GUD. Among men with GUD at baseline compared with those without GUD, the odds ratios were 2.52 for HSV-2, 2.02 for H. ducreyi, 0.97 for syphilis, and 2.14 for HIV. In the second study, HIV-infected men were significantly more likely than HIV-negative men to have antibodies to HSV-2 and H. ducreyi and a history of syphilis or gonorrhea. In the third study, men who converted to HIV were significantly more likely to have antibodies to H. ducreyi and HSV-2 at the visit before seroconversion than those who remained HIV-negative. Two independent predictors of seroconversion--HSV-2 seropositivity before conversion and 10 or more lifetime sexual partners--were identified. In northern Thailand, GUD, especially H. ducreyi and HSV-2, may be both a marker for increased HIV risk and a cofactor for HIV transmission.

The characteristic site-specific reactivation phenotypes of HSV-1 and HSV-2 depend upon the latency-associated transcript region.

After replication at sites of initial inoculation, herpes simplex virus type 1 and 2 (HSV-1 and HSV-2) establish lifelong latent infections of the sensory and autonomic neurons of the ganglia serving those sites. Periodically, the virus reactivates from these neurons, and travels centripetally along the neuronal axon to cause recurrent epithelial infection. The major clinically observed difference between infections with herpes simplex virus type 1 and type 2 is the anatomic site specificity of recurrence. HSV-1 reactivates most efficiently and frequently from trigeminal ganglia, causing recurrent ocular and oral-facial lesions, while HSV-2 reactivates primarily from sacral ganglia causing recurrent genital lesions. An intertypic recombinant virus was constructed and evaluated in animal models of recurrent ocular and genital herpes. Substitution of a 2.8-kbp region from the HSV-1 latency-associated transcript (LAT) for native HSV-2 sequences caused HSV-2 to reactivate with an HSV-1 phenotype in both animal models. The HSV-2 phenotype was restored by replacing the mutated sequences with wild-type HSV-2 LAT-region sequences. These sequences or their products must act specifically in the cellular environments of trigeminal and sacral neurons to promote the reactivation patterns characteristic of each virus.