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Úlcera de la Córnea/terapia , Adhesivos , Vendajes , Dilatación/instrumentación , Femenino , Humanos , Persona de Mediana EdadAsunto(s)
Oftalmopatías/patología , Hidroa Vacciniforme/patología , Niño , Ojo/patología , Humanos , MasculinoRESUMEN
AIMS: To determine whether herpes simplex keratitis (HSK) has declined as an indication for penetrating keratoplasty (PKP) at the University of California San Francisco (UCSF) over the past 30 years. METHODS: Records of the Hogan Eye Pathology Laboratory were reviewed to determine the incidence of PKP performed for HSK from 1972 through 2001. Archived corneal tissue with the diagnosis of HSK was evaluated for herpes simplex virus (HSV) DNA by polymerase chain reaction (PCR) based assays. RESULTS: The number of corneal buttons submitted with the clinical diagnosis of HSK decreased from 1972 to 2001, while the overall number of PKPs performed did not. The percentage of corneal buttons with a clinical diagnosis of HSK that contained detectable HSV DNA did not change over the course of the study period. CONCLUSION: HSK declined as an indication for PKP from 1972 to 2001 at UCSF. It is unlikely that this decline was the result of improved diagnostic accuracy since detection of HSV DNA in corneal buttons with a clinical diagnosis of HSK was similar at the beginning and end of the study period.
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Queratitis Herpética/epidemiología , Queratoplastia Penetrante/estadística & datos numéricos , Acanthamoeba/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , California/epidemiología , Niño , Córnea/parasitología , Córnea/virología , ADN Protozoario/análisis , ADN Viral/análisis , Humanos , Queratitis Herpética/cirugía , Queratitis Herpética/virología , Persona de Mediana Edad , Simplexvirus/aislamiento & purificaciónRESUMEN
AIM: To determine the disease causing gene defects in two patients with Meesmann's corneal dystrophy. METHODS: Mutational analysis of domains 1A and 2B of the keratin 3 (K3) and keratin 12 (K12) genes from two patients with Meesmann's corneal dystrophy was performed by polymerase chain reaction amplification and direct sequencing. RESULTS: Novel mutations of the K12 gene were identified in both patients. In one patient a heterozygous point mutation (429A-->C = Arg135Ser) was found in the 1A domain of the K12 gene. This mutation was confirmed by restriction digestion. In the second patient a heterozygous 27 bp duplication was found inserted in the 2B domain at nucleotide position 1222 (1222ins27) of the K12 gene. This mutation was confirmed by gel electrophoresis. The mutations were not present in unaffected controls. CONCLUSION: Novel K12 mutations were linked to Meesmann's corneal dystrophy in two different patients. A missense mutation replacing a highly conserved arginine residue in the beginning of the helix initiation motif was found in one patient, and an insertion mutation, consisting of a duplication of 27 nucleotides, was found before the helix termination motif in the other.
Asunto(s)
Distrofias Hereditarias de la Córnea/genética , Duplicación de Gen , Queratinas/genética , Mutación Missense , Secuencia de Bases , Estudios de Casos y Controles , Niño , Análisis Mutacional de ADN , Femenino , Humanos , Queratina-12 , Datos de Secuencia MolecularRESUMEN
AIM: To determine which subtypes of Haemophilus influenzae are most commonly associated with ocular disease, and whether the site of ocular H influenzae infection is correlated with specific subtypes of the organism. METHODS: The biotypes and serotypes of ocular H influenzae isolates collected at the Francis I Proctor Foundation between March 1989 and January 2000 were examined. A total of 62 ocular isolates were retrieved from frozen storage and plated on chocolate agar. Biotypes were assigned based upon the ability of the isolates to produce indole, urease, and ornithine decarboxylase. Capsular subtypes a-f were determined by slide agglutination using commercially available subtype specific antisera. Identified biotypes and serotypes were then analysed with regard to site of infection. RESULTS: Patient age ranged from 1 to 92 years with a median age of 45 years. 38 (61%) of the isolates were biotype II, 23 (37%) were biotype III, and one (2%) was biotype VII. All of the isolates were non-encapsulated and thus serologically non-typable. H influenzae biotype II was found in 28 of 48 (58%) conjunctivitis cases, five of eight (63%) keratitis cases, and two of two (100%) endophthalmitis cases. Biotype III was found in 20 of 48 (42%) conjunctivitis cases, two of eight (25%) keratitis cases, and a single case of dacryocystitis. Biotype VII was associated with one of eight (13%) keratitis cases. CONCLUSION: Most ocular H influenzae isolates appear to be serologically non-typable strains from biotypes II and III, less virulent subtypes that frequently colonise the nasopharynx. In addition, the site of ocular H influenzae infections appears to be largely independent of species subtype.
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Infecciones Bacterianas del Ojo/microbiología , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Conjuntivitis Bacteriana/microbiología , Humanos , Lactante , Queratitis/microbiología , Persona de Mediana EdadAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Herpes Zóster Oftálmico/inmunología , Queratitis/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adulto , Fármacos Anti-VIH/uso terapéutico , Antivirales/uso terapéutico , Recuento de Linfocito CD4 , Herpes Zóster Oftálmico/tratamiento farmacológico , Humanos , Masculino , RecurrenciaRESUMEN
To facilitate genotyping of Toxoplasma gondii in vitreous fluid of patients with severe or atypical ocular toxoplasmosis, polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assays were developed for SAG3 (p43) and SAG4 (p18), 2 single-copy surface antigen genes. Together with strategies for SAG1, SAG2, and B1, multilocus RFLP analyses were performed on PCR-amplified parasite DNA present in 12 clinical specimens. Most samples (8/12) were not infected by type II or type III mouse-avirulent strains. Only 1 type III and 3 type II strains were identified, all from immunosuppressed patients. In 6 otherwise healthy adults and in 1 immunosuppressed patient, the SAG1 allele associated with mouse virulence was amplified. Of 12 samples, 3 possessed true type I strains; 5 of 12 had new recombinant genotypes with alleles typical of type I or III strains at all loci examined. The unusual bias toward type I and/or recombinant genotypes bearing the SAG1 type I allele associated with mouse virulence in immunocompetent adults has important implications for the epidemiology and efficacious treatment of ocular toxoplasmosis.
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Proteínas Protozoarias , Toxoplasma/clasificación , Toxoplasma/genética , Toxoplasmosis Ocular/parasitología , Animales , Secuencia de Bases , ADN Protozoario/análisis , ADN Protozoario/genética , Proteínas Fúngicas , Humanos , Glicoproteínas de Membrana/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADN , Toxoplasma/aislamiento & purificación , Cuerpo Vítreo/parasitologíaRESUMEN
In humans and animal models of herpes simplex virus infection, zosteriform skin lesions have been described which result from anterograde spread of the virus following invasion of the nervous system. Such routes of viral spread have not been fully examined following corneal infection, and the possible pathologic consequences of such spread are unknown. To investigate this, recombinant viruses expressing reporter genes were generated to quantify and correlate gene expression with replication in eyes, trigeminal ganglia, and periocular tissue. Reporter activity peaked in eyes 24 h postinfection and rapidly fell to background levels by 48 h despite the continued presence of viral titers. Reporter activity rose in the trigeminal ganglia at 60 h and peaked at 72 h, concomitant with the appearance and persistence of infectious virus. Virus was present in the periocular skin from 24 h despite the lack of significant reporter activity until 84 h postinfection. This detection of reporter activity was followed by the onset of periocular disease on day 4. Corneal infection with a thymidine kinase-deleted reporter virus displayed a similar profile of reporter activity and viral titer in the eyes, but little or no detectable activity was observed in trigeminal ganglia or periocular tissue. In addition, no periocular disease symptoms were observed. These findings demonstrate that viral infection of periocular tissue and subsequent disease development occurs by zosteriform spread from the cornea to the periocular tissue via the trigeminal ganglion rather than by direct spread from cornea to the periocular skin. Furthermore, clinical evidence is discussed suggesting that a similar mode of spreading and disease occurs in humans following primary ocular infection.
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Enfermedades de la Córnea/virología , Dermatitis Perioral/virología , Infecciones Virales del Ojo/virología , Herpes Simple/virología , Herpesvirus Humano 1 , Adolescente , Animales , Chlorocebus aethiops , Enfermedades de la Córnea/complicaciones , Enfermedades de la Córnea/tratamiento farmacológico , Dermatitis Perioral/prevención & control , Modelos Animales de Enfermedad , Infecciones Virales del Ojo/complicaciones , Infecciones Virales del Ojo/tratamiento farmacológico , Femenino , Eliminación de Gen , Genes Reporteros , Genoma Viral , Herpesvirus Humano 1/enzimología , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/patogenicidad , Humanos , Luciferasas/genética , Masculino , Ratones , Fosfotransferasas/genética , Timidina/metabolismo , Ganglio del Trigémino/virología , Células Vero , beta-Galactosidasa/genéticaRESUMEN
PURPOSE: To report a case of Aspergillus fumigatus keratitis after a laser in situ keratomileusis (LASIK) enhancement procedure. METHOD: Case report. RESULTS: A 56-year-old woman developed an ulcer in the flap 13 days after LASIK enhancement. A 4-week course of fortified antibiotics for a presumed bacterial infection followed. The ulcer progressed, causing 60% thinning of the corneal stroma. A biopsy was performed 5 weeks after onset of symptoms, and antifungal agents were initiated. Cultures showed A. fumigatus. Her cornea perforated after the biopsy, requiring cyanoacrylate and lamellar overlay sutures, but the infiltrate resolved on antifungal agents. CONCLUSION: This report is the first description of Aspergillus keratitis after LASIK. We hypothesize that the infection became established on the stromal bed during surgery and led to melting, anteriorly through the flap and posteriorly through the stroma. Diagnosis was made by a corneal biopsy and inoculation of a wide array of media. This case demonstrates the need to consider atypical organisms, including fungi, in the differential diagnosis of post-LASIK infections when there is no response to therapy and highlights the role of corneal biopsy and flap lifting in the diagnosis of this condition.
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Aspergilosis/microbiología , Aspergillus fumigatus/aislamiento & purificación , Úlcera de la Córnea/microbiología , Infecciones Fúngicas del Ojo/microbiología , Queratomileusis por Láser In Situ/efectos adversos , Antifúngicos/uso terapéutico , Aspergilosis/diagnóstico , Aspergilosis/tratamiento farmacológico , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/tratamiento farmacológico , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Persona de Mediana EdadRESUMEN
The purpose of this study was to determine the prevalence of UL97 resistance mutations in cytomegalovirus (CMV) DNA amplified from the eyes of patients with AIDS and newly diagnosed CMV retinitis. Relevant segments of the CMV UL97 gene were amplified from vitreous humor, after which restriction digest screening was performed for resistance mutations at codons 460, 520, 591, 592, 594, 595, and 603. Mutations were confirmed by DNA sequencing. Vitreous from 21 eyes with AIDS-related non-CMV viral retinitis served as negative controls. CMV DNA was successfully amplified from 195 of 204 eyes. A resistance mutation was found in only a single eye, a T-->G mutation at base 1774, predicting a cysteine to glycine mutation at codon 592. The prevalence of UL97 resistance mutations in the eyes of patients with newly diagnosed CMV retinitis is very low.
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Infecciones Oportunistas Relacionadas con el SIDA/virología , Retinitis por Citomegalovirus/tratamiento farmacológico , Retinitis por Citomegalovirus/virología , Citomegalovirus/genética , Farmacorresistencia Microbiana/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Mutación Puntual , Sustitución de Aminoácidos , Antivirales/uso terapéutico , Secuencia de Bases , Cisteína , Citomegalovirus/efectos de los fármacos , Citomegalovirus/aislamiento & purificación , Cartilla de ADN , ADN Viral/genética , Ganciclovir/uso terapéutico , Glicina , Humanos , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
OBJECTIVE: To describe subretinal fibrosis as a long-term complication of Vogt-Koyanagi-Harada (VKH) disease. DESIGN: Retrospective, clinic-based, cross-sectional study and clinical correlation. PARTICIPANTS: Ten patients with VKH disease and subretinal fibrosis were seen at two uveitis referral centers between 1977 and 1997. INTERVENTION: A review of the historical, clinical, and fluorescein angiographic features was performed. MAIN OUTCOME MEASURES: The prevalence, demographic and clinical features, and time to development of subretinal fibrosis were summarized. RESULTS: Subretinal fibrosis occurred in 20 eyes of 10 patients with VKH disease, an overall prevalence of 8% between the two institutions. Patient age ranged from 16 years to 48 years, with a median of 34.5 years. Five patients were Hispanic, one was mixed Hispanic and American Indian, three were Asian or mixed Asian and Caucasian, and one was African-American. Eight of the 10 patients were men. All patients were in the chronic, recurrent phase of their disease when they had subretinal fibrosis develop, and all patients had recurrent episodes of posterior uveitis. Presenting vision ranged from 20/20 to light perception, with a median acuity of 20/200. All patients were initially treated with oral and topical corticosteroids. Four patients required additional noncorticosteroid immunosuppressive therapy. Time from diagnosis of VKH disease to development of subretinal fibrosis ranged from zero (fibrosis present at time of diagnosis) to 27 years, with a median time of 10 months. The median time from diagnosis of VKH to development of subretinal fibrosis in Hispanic patients was 6.5 months, whereas in non-Hispanic patients it was 6.5 years. Final vision ranged from 20/25 to light perception, with a median acuity of 20/60. Seven of 20 eyes had a final visual acuity of 20/40 or better, and seven eyes saw 20/200 or worse. Five of the eyes with 20/200 or worse vision had fibrosis involving the fovea. CONCLUSIONS: Subretinal fibrosis occurs in a sizeable proportion of patients with VKH disease and may contribute to permanent loss of vision.
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Retina/patología , Enfermedades de la Retina/etiología , Síndrome Uveomeningoencefálico/complicaciones , Adolescente , Adulto , Femenino , Fibrosis , Angiografía con Fluoresceína , Humanos , Masculino , Prevalencia , Enfermedades de la Retina/diagnóstico , Estudios Retrospectivos , Agudeza VisualRESUMEN
Herpetic eye disease is common and is frequently associated with intraocular inflammation or uveitis. Despite recent advances in measuring anti-herpes virus antibodies and viral DNA in ocular fluids, diagnosis remains largely clinical. The two more common syndromes include anterior uveitis, often associated with keratitis, and the acute retinal necrosis (ARN) syndrome. Treatment is complex and requires careful monitoring to provide the appropriate balance of antiviral medication and corticosteroids. Long-term prophylaxis with oral antiviral agents may be required in selected patients to help prevent the vision-compromising complications associated with recurrences.
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Antivirales/uso terapéutico , Infecciones Virales del Ojo , Glucocorticoides/uso terapéutico , Infecciones por Herpesviridae , Uveítis , Técnicas de Diagnóstico Oftalmológico , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/tratamiento farmacológico , Infecciones Virales del Ojo/virología , Infecciones por Herpesviridae/diagnóstico , Infecciones por Herpesviridae/tratamiento farmacológico , Infecciones por Herpesviridae/virología , Humanos , Uveítis/diagnóstico , Uveítis/tratamiento farmacológico , Uveítis/virologíaAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antivirales/efectos adversos , Retinitis por Citomegalovirus/tratamiento farmacológico , Citomegalovirus/efectos de los fármacos , VIH/efectos de los fármacos , Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/virología , Anticuerpos Antivirales/análisis , Recuento de Linfocito CD4 , Citomegalovirus/inmunología , Citomegalovirus/aislamiento & purificación , Retinitis por Citomegalovirus/inmunología , Retinitis por Citomegalovirus/virología , VIH/inmunología , VIH/aislamiento & purificación , Humanos , Estudios Prospectivos , Seguridad , Resultado del Tratamiento , Carga ViralRESUMEN
Productive infection with herpes simplex virus (HSV) type 1 is limited by both innate and adaptive immune mechanisms. The purpose of the current study was to determine whether these mechanisms also play a role in the establishment of latent HSV infection. First we examined the trigeminal ganglia (TG) of severe combined immunodeficiency (SCID), interferon-gamma knockout (GKO), and beige (a strain deficient in natural killer cell activity) mice following ocular inoculation with HSV. Although infection of SCID mice was invariably lethal, we consistently found latently infected neurons in the TG of these animals at 2-4 days postinoculation. HSV infection of GKO and beige mice, while not lethal, was characterized by a greater number of productively infected TG neurons and/or a delay in the time to peak productive infection compared to C57BL/6 controls. However, as assayed by both in situ hybridization for LAT expression and quantitative PCR (Q-PCR) for viral DNA, we found that HSV established a latent infection in GKO and beige mice as efficiently as in C57BL/6 controls. We subsequently examined the TG of "HSV-sensitive" strains of mice (Swiss-Webster, CBA, and BALB/c) following ocular infection with HSV. At the peak of acute ganglionic infection the number of productively infected TG neurons in each of these mouse strains was about sevenfold greater than in the "HSV-resistant" strain C57BL/6, consistent with previously reported differences in susceptibility to lethal challenge with HSV. However, as assayed by both in situ hybridization for LAT and Q-PCR for viral DNA, we found that HSV established a latent infection in Swiss-Webster, CBA, and BALB/c mice as efficiently as in C57BL/6 controls. We conclude that HSV efficiently establishes latent infection in the TG of mice in the absence of innate and adaptive immune mechanisms that are essential for limiting productive viral infection.
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Herpes Simple/inmunología , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 1/fisiología , Ganglio del Trigémino/virología , Animales , Linfocitos B/inmunología , ADN Viral/análisis , Susceptibilidad a Enfermedades , Herpes Simple/virología , Inmunidad Innata , Interferón gamma/genética , Interferón gamma/inmunología , Péptidos y Proteínas de Señalización Intracelular , Células Asesinas Naturales/inmunología , Ratones , Ratones Endogámicos , Ratones Noqueados , Ratones SCID , Neuronas/virología , Proteínas/genética , ARN Viral/análisis , Linfocitos T/inmunología , Proteínas de Transporte Vesicular , Latencia del VirusRESUMEN
PURPOSE: The primary goal of this study was to determine the viral cause of the acute retinal necrosis syndrome in 28 patients (30 eyes). A secondary goal was to investigate possible associations between viral cause and patient age, and viral cause and central nervous system disease. METHODS: A retrospective case series in which we reviewed the laboratory results and clinical histories of 28 patients (30 eyes) diagnosed with acute retinal necrosis syndrome, from whom vitreous or aqueous specimens were received, for diagnostic evaluation using previously described polymerase chain reaction-based assays. RESULTS: Varicella-zoster virus, herpes simplex virus, and cytomegalovirus (CMV) DNA were detected in aqueous and/or vitreous specimens from 27 of 28 patients (29 of 30 eyes with a clinical history of acute retinal necrosis syndrome). No sample was positive for DNA from more than one virus. Varicella-zoster virus DNA was detected in 13 patients (15 eyes). Median age was 57 years. Herpes simplex virus type 1 DNA was detected in seven patients (seven eyes). Median age was 47 years. Six of these patients had a history of herpes simplex virus encephalitis. Herpes simplex virus type 2 DNA was detected in six patients (six eyes). Median age was 20 years. Three of these patients had a likely history of meningitis. Cytomegalovirus DNA was detected in one patient who was immunosuppressed iatrogenically. No viral DNA was detected in one patient from whom a sample was taken after 6 weeks of acyclovir therapy. CONCLUSIONS: The data suggest that varicella-zoster virus or herpes simplex virus type 1 cause acute retinal necrosis syndrome in patients older than 25 years, whereas herpes simplex virus type 2 causes acute retinal necrosis in patients younger than 25 years. A history of central nervous system infection in a patient with acute retinal necrosis syndrome suggests that herpes simplex virus is likely to be the viral cause.
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Infecciones por Citomegalovirus/complicaciones , Infecciones Virales del Ojo/complicaciones , Herpes Simple/complicaciones , Herpes Zóster Oftálmico/complicaciones , Síndrome de Necrosis Retiniana Aguda/etiología , Adolescente , Adulto , Factores de Edad , Anciano , Humor Acuoso/virología , Niño , Citomegalovirus/genética , ADN Viral/análisis , Encefalitis por Herpes Simple/complicaciones , Femenino , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Herpesvirus Humano 3/genética , Humanos , Masculino , Meningitis Viral/complicaciones , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Cuerpo Vítreo/virologíaAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Fármacos Anti-VIH/uso terapéutico , Retinitis por Citomegalovirus/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/virología , Adulto , Retinitis por Citomegalovirus/tratamiento farmacológico , Retinitis por Citomegalovirus/virología , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
We characterized the populations of primary sensory neurons that become latently infected with herpes simplex virus (HSV) following peripheral inoculation. Twenty-one days after ocular inoculation with HSV strain KOS, 81% of latency-associated transcript (LAT)-positive trigeminal ganglion (TG) neurons coexpressed SSEA3, 71% coexpressed Trk(A) (the high-affinity nerve growth factor receptor), and 68% coexpressed antigen recognized by monoclonal antibody (MAb) A5; less than 5% coexpressed antigen recognized by MAb KH10. The distribution of LAT-positive, latently infected TG neurons contrasted sharply with (i) the overall distribution of neuronal phenotypes in latently infected TG and (ii) the neuronal distribution of viral antigen in productively infected TG. Similar results were obtained following ocular and footpad inoculation with KOS/62, a LAT deletion mutant in which the LAT promoter is used to drive expression of the Escherichia coli lacZ gene. Thus, although all neuronal populations within primary sensory ganglia appear to be capable of supporting a productive infection with HSV, some neuronal phenotypes are more permissive for establishment of a latent infection with LAT expression than others. Furthermore, expression of HSV LAT does not appear to play a role in this process. These findings indicate that there are marked differences in the outcome of HSV infection among the different neuronal populations in the TG and highlight the key role that the host neuron may play in regulating the repertoire of viral gene expression during the establishment of HSV latent infection.