Herpes Simplex Virus Isolates Research Articles

Herpes Simplex Keratitis in South India: Clinico-Virological Correlation

Purpose: A retrospective cross-section study to analyze the prevalence of herpes simplex virus–induced keratitis (HSK) among 3,000 patients attending a corneal clinic in South India between 1995 and 1997, and to evaluate laboratory techniques for detecting HSK. Methods: The clinico-virological correlation was studied using herpes simplex virus (HSV) isolation on the Vero cell line, HSV-specific antigen detection by indirect immunofluorescence (IF) microscopy, and serum anti-HSV IgG quantitation, IgM estimation, and tear secretory IgA (sIgA) detection by ELISA. Observations: HSK had a prevalence of 7.8% (234 patients) in this study. A virological correlation could be obtained in 44.4% of the cases that had epithelial manifestations and in 14.8% of the cases that had only stromal disease. In 161 cases where both culture and IF microscopy were used, IF detected 27 cases (26.8%) more than cell culture. The difference in sensitivity between cell culture and IF was found to be statistically significant (McNemar's test, P < .05). An elevation in IgG titer was seen in 17 (30.4%) cases. IgM was detected in only 2 cases of the 62 (3.2%) analyzed. Of the 138 cases analyzed, sIgA was positive in 28 (20.3%) cases. A proved diagnosis could be made in 58% of cases when the specimen was collected during the first week after disease onset, and in only 5% when the time interval increased to 4 weeks. Conclusions: HSV antigen detection by indirect IF is a rapid and sensitive diagnostic tool for HSK. Tear secretory IgA (sIgA) is a specific marker for acute herpetic keratitis, and the detection of HSV-specific tear sIgA is a valuable adjunct to virus isolation and antigen detection in the laboratory diagnosis of HSK. For a successful diagnosis, the specimen should be collected as soon as possible after HSK onset.

Herpes simplex and intensive care medicine: an underestimated problem?

Herpes Simplex Virus (HSV) infection may cause different disorders in patients hospitalised in intensive care. Bronchoalveolar lavage (BAL is a procedure performed almost as a routine in patients with unexplained respiratory insufficiency in our department. During the last 10 years, HSV has been isolated frequently from the respiratory tract at our 30 beds intensive care unit. The objectives of this retrospective study were to define risk factors of the population in whom HSV virus was isolated. The study concerned patients with an isolation of HSV from either bronchial aspiration (BA) or BAL in the past 5 years (1992–1997). HSV was isolated by culture on shell vials and identified by immunofluorescence after staining with monoclonal antibodies or by the conventional culture and cytopathogenic effect on Vero-cells. From the 64 cases observed, 47 HSV isolations originated from BA, 13 from BAL (of which 9 with simultaneously negative BA) and 4 from both BA and BAL. The mean age of the patients was 62 years (range from 16 to 82). Only 50% of the patients had fever at the time of the investigation. The majority of the patients (94.9%) was intubated before the isolation. The role of immunosuppression, previously recognized as a risk factor for herpes infection, was not confirmed in this study: only 20.4% had received cither corticosteroids or immunosuppressive agents. Striking is that 73.4% had undergone a surgical procedure before the isolation, mainly coronary bypass grafting or other thoracic operations. Daily chest X-rays from 2 days before till 2 days after virus isolation were reviewed blindly by the same radiologist. There was no pathognomonic image at the chest X-ray: a localized infiltrate resembling pneumonia, diffuse alveolar infiltrates or an interstitial pattern were observed and 14% of the chest X-rays were even defined as normal. Lung injury was severe: almost 60% had a PaO2/FiO2 less than 200. 28 patients received aciclovir therapy once herpes was isolated, without an effect on the outcome: 48.4% of all patients and 42.8% of those receiving aciclovir therapy (28) died. Isolation of HSV in respiratory samples from critically ill patientsis therefore more frequent than previously known. Whether these isolates contribute to illness and its evolution remains to be determined.

Tear secretory IgA: evaluation of usefulness as a diagnostic marker in herpetic keratitis

In a South Indian study, an `in-house' enzyme-linked immunosorbent assay (ELISA) was developed to evaluate the potential of herpes simplex virus (HSV)-specific tear secretory IgA (sIgA) in the diagnosis of herpes simplex keratitis (HSK). The presence of HSV-specific tear sIgA was found to be diagnostic in 20.28% of cases. The usefulness of the sIgA ELISA system was evaluated against HSV isolation, which is the `gold standard' and HSV antigen detection, a more sensitive, commonly employed method. Analysis of HSV-specific IgG and IgM results showed their failure as reliable indicators of active or ongoing infection. Comparison of sIgA ELISA with culture as `gold standard' showed its sensitivity, specificity, and positive and negative predictive values to be 60% (95% CI 36.4-80), 93.2% (95% CI 86.7-96.8), 60% (95% CI 36.4-80), and 93.2% (95% CI 86.7-96.8), respectively. This study is the first report on the complete evaluation of the usefulness of tear anti-HSV sIgA in the laboratory diagnosis of HSK, taking into account both epithelial and stromal keratitis cases.

Detection of herpes simplex virus DNA in semen of men with genital HSV-2 infection.

Previous studies, using viral culture, have suggested that herpes simplex virus (HSV) isolation from semen is rare. This study attempts to investigate further the role of semen in sexual transmission of HSV. To evaluate semen samples for HSV DNA with a sensitive polymerase chain reaction (PCR) test. Laboratory examination of 255 stored semen samples collected from 15 healthy men with genital HSV-2 infection during a prospective clinical trial. Herpes simplex virus DNA was detected in 8 (3.1%) semen samples, 6 of which were collected during a herpes recurrence. Herpes simplex virus DNA was not detected in any of the 18 samples collected during acyclovir therapy. Herpes simplex DNA can be detected in semen, although it appears closely associated with clinical HSV reactivation. More detailed studies will be needed to assess the role HSV-2 in semen plays in transmission of infection.

Phenotypic and genotypic characterization of acyclovir-resistant herpes simplex viruses from immunocompromised patients.

Phenotypic and genotypic analyses were done on 30 acyclovir-resistant and 5 acyclovir-susceptible herpes simplex virus (HSV) isolates (22 HSV type 1 and 13 HSV type 2) recovered from 24 subjects. All isolates were susceptible to foscarnet. The phenotypes of the acyclovir-resistant HSV isolates were as follows: 17 were thymidine kinase (TK) deficient, 12 had decreased TK activity (produced low amounts of viral TK) or TK with altered substrate specificity, and 1 was undetermined. Sequencing analysis of the HSV TK gene revealed that 14 (46.7%) of 30 acyclovir-resistant isolates had an insertion or deletion of 1 or 2 nucleotides, especially in homopolymer runs of Gs, Cs, and rarely in As. On the other hand, 16 (53.3%) of 30 acyclovir-resistant isolates had point mutations in conserved or nonconserved regions of the TK gene. In conclusion, HSV can develop multiple strategies to exhibit acyclovir resistance, including, in about half of the cases, frameshift mutations in homopolymer nucleotide stretches of the TK gene.

A comparison of PCR with virus isolation and direct antigen detection for diagnosis and typing of genital herpes

Patients attending the genitourinary medicine clinic at Watford General Hospital, UK, were examined for clinical signs of genital herpes infection. Genital swabs were taken from 194 patients (126 female, 68 male) who presented with genital ulceration or symptoms which were suggestive of genital herpes infection. Swabs from these patients were tested by three methods: (i) Detection of herpes simplex virus (HSV) antigen by direct HSV enzyme immunoassay (EIA), (ii) HSV isolation in Vero cell culture and (iii) HSV polymerase chain reaction (PCR). HSV was detected in 76 patients (39%) by EIA, in 93 (48%) by isolation in cell culture, and in 115 (59%) by PCR. Isolation by cell culture has been considered as the "gold standard" for the detection of HSV in genital lesions, but in this study HSV PCR was significantly more sensitive. Comparison of the three methods was as follows: Cell culture vs. PCR: Sensitivity 93/115 (80.9%), Specificity 79/79 (100%). HSV EIA vs. PCR: Sensitivity 75/115 (65.2%), Specificity 78/79 (98.7%). HSV EIA vs. Cell culture: Sensitivity 75/93 (80.7%), Specificity 100/101 (99%). EIA was less effective in detecting HSV among recurrent than among first episode infections, in comparison to culture or HSV PCR. This is the first comparison of HSV PCR with two other routine diagnostic methods for confirming genital herpes infection in a symptomatic population. The infecting HSV type was identified by restriction digestion of 108 HSV amplicons: HSV-1:37/108 (34%), HSV-2:71/108 (66%). In this population HSV-1 causes a significant proportion of genital herpes cases, and HSV-1 genital infection was detected in significantly more first episode infections (40.3%) than among recurrent infections (22.2%).

Survey of resistance of herpes simplex virus to acyclovir in northwest England.

Acyclovir (ACV) has been used for more than 15 years in the management of herpes simplex virus (HSV) and varicella-zoster virus (VZV) disease. The present survey was undertaken to assess the level of ACV resistance in the population. More than 2,000 HSV isolates from both immunocompetent and immunocompromised patients in northwest England were collected over a 2-year period and tested for sensitivity to ACV. These studies suggested a prevalence of resistance of approximately 0.1 to 0.6% in immunocompetent individuals, with no apparent difference in prevalence between treated and untreated groups. In line with previous studies, the prevalence of resistance in treated immunocompromised individuals was approximately 6%.

Evidence of latency and reactivation of both herpes simplex virus (HSV)-1 and HSV-2 in the genital region.

While superinfection with different herpes simplex virus (HSV) types has been demonstrated in animals, the ability of the two HSV types to colonize and reactivate in the same anatomic region in humans has not been well demonstrated. In 6 patients, both HSV-1 and HSV-2 was recovered from genital lesions. In 4 of them, who initially acquired genital HSV-1 infection, subsequent HSV-2 infection presented as a prolonged episode of genital lesions and a marked increase in the frequency of genital recurrences. While most of the subsequent clinical reactivations were HSV-2, in 2 patients the recurrence rate of genital HSV-1 increased after the acquisition of HSV-2. These data demonstrate the ability of a second HSV type to infect the same anatomic region and illustrate the difference in reactivation frequency of the two types in the same person. Typing of HSV isolates may be useful in persons with recent alteration in recurrence rates of genital HSV.

Herpes simplex viruses.

Herpes simplex virus (HSV) infections of humans have been documented since the advent of writing. The spectrum of disease was expanded to include primary and recurrent infections of mucous membranes (gingivostomatitis, herpes labialis, and genital HSV infections), keratoconjunctivitis, neonatal HSV infection, visceral HSV infections of the immunocompromised host, HSV encephalitis, Kaposi's varicella-like eruption, and an association with erythema multiforme. Cumulative experience suggests that factors associated with pregnancy may place both the mother and fetus at increased risk for severe infection, possibly because of altered cell-mediated immunity. The major risk to the fetus is with primary or initial genital HSV infection of the mother. PCR evaluation of cerebrospinal fluid can be utilized to monitor therapeutic outcome in patients with herpes simplex encephalitis. The use of HSV for gene therapy heralds a new era of herpes biology, the conversion of a hazardous foe into a user-friendly surgical tool. Asymptomatic shedding of virus can continue despite clinically effective suppression with acyclovir, so the possibility of person-to-person transmission persists. Newborns with HSV infections can be classified as having disease that is localized to the skin, eyes, and mouth; affects the central nervous system (CNS); or is disseminated. Drug resistance was considered rare and resistant isolates were thought to be less pathogenic until a series of acyclovir-resistant HSV isolates from patients with AIDS were characterized. The risk of nephrotoxicity can be minimized by administering acyclovir by slow infusion and ensuring adequate hydration.

Herpes Simplex Virus Latency after Direct Ganglion Virus Inoculation

Herpes simplex virus (HSV) latent infection of ganglion neurons follows axoplasmic transport of HSV, probably in the form of nucleocapsid from peripheral sites of infection (e.g. footpad). This raises the possibility that latency is dependent on this particular means of presenting HSV to ganglion neurons. To investigate this, we directly infected ganglia of mice with HSV and evaluated latency. Initially, ganglia were surgically exposed in intact mice, infected with HSV and after 4 weeks evaluated for HSV latency-associated transcript (LAT) expression. LAT expression suggested latency. To more fully evaluate latency after direct ganglion inoculation, a transplant model was developed. In this model, ganglia were removed from mice, inoculated with HSV, transplanted into syngeneic recipients and evaluated for latency after several weeks. Latency was evident in transplanted ganglia by (1) the presence of LAT in neurons; (2) the lack of HSV ICP4 RNA or viral antigen, and (3) the isolation of HSV from explants of transplants but not from direct homogenates. The transplant model was then used to evaluate the effect of inhibition of HSV replication on latency. Antivirals which inhibited HSV replication markedly decreased the number of LAT-positive neurons in transplants, suggesting a role for HSV replication mechanisms and latency. It is thought that direct ganglion inoculation and ganglion transplant methods will permit unique investigations of mechanisms of latency.

A Rapid Assay to Screen for Drug‐Resistant Herpes Simplex Virus

A rapid assay was developed to screen for herpes simplex virus (HSV) isolates that are resistant to acyclovir and other antiviral agents. The assay is a modified plaque reduction assay (PRA) in which the number of plaques seen in the absence of acyclovir was compared with that seen in the presence of a single cutoff concentration of acyclovir (2 microg/mL). This assay utilizes a cell line that expresses beta-galactosidase only after infection with HSV. Since histochemically stained plaques are easily visualized, small plaques can be easily enumerated. This allows the assay to be performed on dilutions of untitered specimens in the small wells of a 24-well plate and allows the results to be read only 2 days after inoculation of the virus. The assay performed well compared with a standard PRA and should be a valuable tool in identifying drug-resistant HSV in a timely manner.

Guidelines of care for dermatologic conditions in patients infected with HIV

Guidelines of care for dermatologic conditions in patients infected with HIV

Clinical Considerations when Herpes Simplex Virus Is Isolated from Bronchoscopy Specimens

The purpose of this pilot study was to define the clinical relevance of herpes simplex virus (HSV) isolated from bronchoscopy specimens. A retrospective review of clinical characteristics, bronchoscopic features and outcome for 40 patients (24 patients with Acquired Immunodeficiency Syndrome (AIDS), 16 without AIDS) was conducted during an 18 month period in a major university hospital. HSV was isolated from bronchoscopy specimens from all patients in the study. Procedures included flexible fiberoptic bronchoscopy with bronchoalveolar (BAL) washings, brushings and/or bronchoscopic lung biopsy. Hospital records, clinical studies, potential risk factors for HSV infection, and results of bronchoscopic examination were reviewed. 20 patients were hospitalized in the Intensive Care Unit (4 with AIDS, 16 without AIDS). Bronchoscopy revealed raised white plaques with surrounding erythema in the airways of 17 (42.5%) patients. Other potentially pathogenic organisms were present in 30 patients (75%). Cytology revealed inflammation in 2 (8.3%) patients with AIDS and in 9 (56.3%) patients without AIDS. HSV-like cellular changes, however, were seen in only 14 patients (5 with AIDS, 9 without AIDS). The isolation of HSV from bronchoscopy specimens may have different clinical relevance for patients, depending upon host immune status and other underlying illnesses. Regardless, the determination of the clinical relevance of HSV isolation in bronchoscopy specimens is complex. The full spectrum of HSV-related lower respiratory infections can only be addressed by well-designed, prospective studies that address histopathology, operating characteristics of bronchoscopic appearance, selective sampling of various parts of the respiratory tract, and specific antiviral therapy.

Evaluation of the range of clinical presentations of herpes simplex encephalitis by using polymerase chain reaction assay of cerebrospinal fluid samples.

Detection of DNA from herpes simplex virus in cerebrospinal fluid (CSF) samples by polymerase chain reaction (PCR) analysis has been shown to be more sensitive and specific for the diagnosis of herpes simplex encephalitis than isolation of herpes simplex virus from biopsy specimens of brain tissue. Because of the invasiveness of brain biopsy, it has been suggested that PCR analysis of CSF may reveal a wider spectrum of the disease than has been previously recognized by brain biopsy studies. In this study, PCR assay of CSF samples obtained from 29, 12, and 8 patients with focal, mild, and diffuse encephalitis, respectively, was performed. PCR assay was positive for 15 (51.7%) of 29 patients with focal encephalitis and three (25%) of 12 patients with mild encephalitis. The correlation between temporal abnormalities shown by electroencephalography, computed tomography of the brain, or cranial magnetic resonance imaging and a positive PCR assay was high. PCR analysis has revealed that atypical and less severe forms of encephalitis are caused by herpes simplex virus.

Pathogenicity of glycoprotein C-deficient herpes simplex virus 1 strain TN-1 which encodes truncated glycoprotein C.

A clinical isolate of herpes simplex virus 1 (TN-1) from a stromal keratitis patient was found to be defective in the glycoprotein C (gC) gene (UL44), thus resulting in the production of truncated gC upon infection. To study the pathogenetic role of truncated gC, we prepared a recombinant LTN-8 derived from TN-1 with deletions of the 1.5 kilobase pairs of the gC gene including the initiation codon. A penetration assay revealed LTN-8 to be less efficient in its penetration ability than TN-1, the laboratory strain KOS and RTN-1-20-3, a recombinant derived from TN-1 with the KOS gC gene. The penetration of LTN-8 was facilitated by the addition of TN-1-infected culture medium. TN-1 virus preparations had no hemagglutinating activity. However, the animals infected with TN-1 did develop hemagglutination inhibition (HI) antibodies. The LTN-8-infected animals did not develop HI antibodies. The pathogenicity in BALB/c mice following either corneal, intraperitoneal or intracerebral inoculation did not significantly differ among TN-1, RTN-1-20-3 or LTN-8. Our results indicate that truncated gC was sufficient for the induction of HI antibodies and was also able to facilitate penetration in vitro. Although truncated gC might be a virulence factor acting as a decoy, both truncated gC and intact gC had little effect on the outcome following intracerebral, intraperitoneal or corneal inoculation.

Bell's palsy and herpes simplex virus.

Bell's palsy, which is defined as idiopathic peripheral facial paralysis of sudden onset, accounts for > 50% of all cases of facial paralysis. Different theories on the etiology of Bell's palsy have been proposed and investigated. Various clinical studies have suggested an etiological link between Bell's palsy and herpes simplex virus (HSV). In addition, animal experiments have shown the ability of HSV to induce facial paralysis. In our opinion, the possible link between Bell's palsy and HSV can only be explored properly by studying the human facial nerve, and especially the geniculate ganglion itself. Different groups have tried to detect hypothetically reactivated and hypothetically latent HSV in the facial nerves of Bell's palsy patients and control patients, respectively. The isolation of infectious HSV from facial nerve tissue by conventional cell culture methods appeared to be very difficult, also when Bell's palsy patients were tested. Instead, modern molecular methods, such as in situ hybridization and the polymerase chain reaction (PCR) could easily detect HSV DNA in geniculate ganglia. The detection of HSV-specific latency-associated transcripts in the ganglia of control patients provided further evidence for the hypothetically latent state of HSV in the geniculate ganglia in these patients. Recent PCR experiments performed by a Japanese group strongly suggest that the area adjacent to the geniculate ganglia does not usually contain any HSV at all, except in patients with Bell's palsy. This well-controlled study provides conclusive evidence that reactivation of HSV genomes from the geniculate ganglia is the most important cause of Bell's palsy. Consequently, it has been suggested that "Bell's palsy" be renamed as "herpetic facial paralysis".

A system for isolation, transport and storage of herpes simplex viruses

A major difficulty with diagnostic virus isolation concerns the relative thermolability of certain viruses, e.g. herpes simplex virus type 2, which may, therefore, lose infectivity during transport to the laboratory. This study describes a system of virus isolation and transport, which depends on direct inoculation at the bedside or clinic, to a monolayer or suspension of susceptible cells with subsequent incubation for 10 h at approximately 32 °C, whereupon the newly synthesised virus becomes very stable if the cells are subsequently maintained at room temperature. This system was found to increase the sensitivity of isolation of herpes simplex virus, particularly under conditions of asymptomatic virus excretion or if there was significant delay in transportation of clinical samples to the virus laboratory. It is envisaged that this system will allow clinical self-sampling by the patient with application to epidemiological surveys in both the developed and underdeveloped world.

Asymptomatic Perianal Shedding of Herpes Simplex Virus in Patients With Acquired Immunodeficiency Syndrome

To determine the frequency of asymptomatic perianal shedding of herpes simplex virus (HSV) in adult patients with acquired immunodeficiency syndrome (AIDS). Cross-sectional study. A 1000-bed, state-supported hospital in Brazil that provides comprehensive health care. Eighty-two consecutively hospitalized patients with AIDS (Centers for Disease Control and Prevention class C). Specimens for HSV culture were obtained with premoistened swabs of the perianal region at approximately 7-day intervals during the hospitalization of each patient. After the specimens were inoculated into cultures of human foreskin and Vero cells, supernatants of cultures showing the cytopathic effect characteristic of HSV infection were tested for virus in a confirmatory immunoenzymatic assay. Typing of HSV was performed by polymerase chain reaction amplification of HSV-1- and HSV-2-specific DNA polymerase sequences. On early into the study, 12 (15%) of 82 patients had perianal ulceration and 70 did not. None of the patients in the latter group developed perianal ulcers during the study period, but HSV was isolated at least once from 17 (24%) of them. Nine of the 17 asymptomatic perianal shedders had a mean of 3 perianal swabs collected before the first HSV isolation, and 11 (65%) of 17 had a total of 18 perianal swabs collected 8 to 62 days after the HSV isolation. All postpositive samples were negative for HSV except 1 obtained from a patient 13 days after the first positive sample. Twelve of the 17 asymptomatic perianal shedders of HSV were followed up clinically for 8 to 62 days after the first episode of shedding and none developed perianal ulceration. We conclude that asymptomatic perianal shedding of HSV is common in patients with AIDS, even among those without a history of perianal HSV lesions. This shedding appears to be short-lived, intermittent, and not associated with early subsequent development of perianal ulcers. These findings present a new perspective on the natural course of perianal HSV infection in patients with AIDS.

Comparison of a DNA probe assay with the plaque reduction assay for measuring the sensitivity of herpes simplex virus and varicella-zoster virus to penciclovir and acyclovir

A DNA probe assay was compared with the plaque reduction assay to determine the sensitivity of clinical isolates of herpes simplex virus (HSV) and varicella-zoster virus (VZV) to penciclovir and acyclovir in MRC-5 cells. In both assays, penciclovir and acyclovir shared comparable activity against cell-free virus (CFV) preparations of VZV and herpes simplex virus type 1 (HSV-1) isolates, whilst acyclovir was significantly more active than penciclovir against herpes simplex virus type 2 (HSV-2) isolates in both the DNA probe assay (P < or = 0.01) and the plaque reduction assay (P < or = 0.01). However, the 50% effective concentrations (EC50s) were generally lower in the DNA probe assay and the correlation between the plaque reduction and DNA probe assays was poor for either compound. Six acyclovir-resistant strains of HSV-1 derived in cell culture were also tested for susceptibility to penciclovir and acyclovir, in the DNA probe and plaque reduction assays. The relative susceptibilities of these strains were comparable, for example, one ACV-resistant strain was susceptible to penciclovir in both assays. Further comparisons of the assay methods were made using cell-associated VZV (CAV). As with CFV the EC50s were significantly lower in the DNA probe assay than the plaque reduction assay for penciclovir (P < or = 0.01) and acyclovir (P < or = 0.01). In the DNA probe assay there was no significant difference in the EC50s for either penciclovir or acyclovir when comparing CAV with CFV. However, in the plaque reduction assay the EC50s for CAV were significantly higher than those for CFV for both penciclovir (P < or = 0.01) and acyclovir (P < or = 0.01). Overall the DNA probe assay is objective, does not require prior titration of isolates and provides opportunities for automation. It is more suitable for sensitivity testing of large numbers of clinical isolates than the well-established plaque reduction assay.

Neuroinvasive properties of herpes simplex virus type 1 glycoprotein variants are controlled by the immune response.

Neuroinvasiveness is a property central to the pathogenesis of herpes simplex virus (HSV) and most isolates demonstrate this property. Exceptions are HSV strains KOS and ANG, for which we have previously shown that the non-neuroinvasive phenotype is referable to single amino acid changes in glycoprotein D for ANG or glycoprotein B for KOS. Because glycoproteins B and D are immunologically significant, the possibility that the phenotype has an immunologic basis was examined. Nonimmunosuppressed mice could not be killed with any dose of these non-neuroinvasive viruses after footpad inoculation, but in cyclophosphamide-suppressed animals, the ratios of plaque-forming units to LD50 decreased by at least four orders of magnitude to levels comparable with that of ANG-path, a neuroinvasive derivative of ANG. KOS and ANG induced a more rapid circulating neutralizing Ab response than did ANG-path, and mice were protected when these agents were co-infected with the neuroinvasive strain. The noninvasive viruses engendered an enhanced mononuclear cell infiltrate in infected spinal ganglia which consisted of increased numbers of CD4+ and CD8+ T cells and an increased production and secretion of IgG. HSV-specific Ab-secreting cells were also observed. In addition, passive transfer of anti-HSV mouse serum protected immunosuppressed mice from lethal HSV challenge. Selective in vivo depletion of T lymphocytes increased the detectable levels of both KOS and ANG viruses in the spinal ganglia at 6 days postinfection, but it did not alter the ratios of plaque-forming units to LD50 or affect the HSV-induced increase in ganglionic IgG. Taken together, these data indicate that in these systems there is an immunologic basis for the control of HSV-1 neuroinvasiveness and that humoral, rather than cell-mediated immunity, is playing the major role.