Herpes simplex virus type I encephalitis with left temporal lobe lesion detected by gadolinium enhanced MRI

A case of herpes simplex virus (type I, HSV-I) encephalitis (HSE) was reported. A 65 years old man presented acute fever and subsequently developed mental symptoms, disorientation and consciousness disturbance. HSV-I antibody titers of serum and CSF were markedly elevated, especially the elevation of IgM antibody was noticeable. MRI T1 weighted image enhanced by Gadolinium DTPA taken on the 15th day from the onset revealed a lesion in the inner side of left temporal lobe. Acyclovir therapy was administered under the diagnosis of HSE. He recovered well with the residual of moderate memory disturbance. This is a very interesting and rare case of HSE in an old patient caused by the primary infection of HSV-I. In addition, the importance of Gd enhanced MRI study to detect HSE lesion was discussed.     

巢式PCR与ABC-ELISA检测单纯疱疹病毒的比较

在Ⅰ型单纯疱疹病毒（HSV－I）TK基因的保守区域设计3个引物，建立巢式PCR方法。敏感性实验显示巢式PCR比单一PCR敏感500倍。用巢式PCR法和ABC－ELISA法平行检测30例临床诊断为单纯疱疹病毒性脑炎（HSE）患者和20例非中枢神经系统感染患者的脑脊液（CSF）标本。结果表明两种方法特异性完全一致，然巢式PCR的敏感性较高。30例HSE中巢式PCR的检出阳。性率为87％（26／30），ABC－ELISA为77％（23／30），且巢式PCR于检查当日即可获得阳性结果。提示其更适用于HSE的早期诊断。     

Human T-cell lymphotropic virus tax and Epstein-Barr virus DNA in peripheral blood of multiple sclerosis patients during acute attack

Objectives - A study was performed to determine whether persistent or latent viruses are reactivated during the acute attack in relapsing remitting multiple sclerosis (MS). Material and methods - DNA of herpes simplex virus type 1 and 2 (HSV-1 and -2), human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), JC virus (JCV) and HTLV-I was searched, using nested polymerase chain reaction (PCR), in peripheral blood mononuclear cells (PBMCs) collected from 14 MS patients on the first day and, twice a week, during an acute attack of the disease. Results -Viral DNA was detected, in at least one PBMC sample, in all the patients. Interestingly, EBV DNA was found in 42.8% of the patients on the first day, while a sharp increase of the HTLV tax-rex DNA frequency (35.7%) was observed on the tenth day. Conclusions - In MS relapse EBV DNA detection is an early, frequent event, while the finding of tax-rex , but not of other HTLV-I genomic regions, is a secondary phenomenon, suggesting that these two factors could interact in the pathogenesis of MS relapses.     

Feline immunodeficiency virus associated myopathy in the adult cat

Human immunodeficiency virus (HIV-1) associated myopathy can be a debilitating disease in humans, leading to weakness, myalgia, and muscle wasting. Subclinical neuromuscular involvement is also common. A range of histologic lesions have been described in both forms that include both inflammatory and degenerative changes. The purpose of this study was to determine whether a myopathy was present in adult cats experimentally infected with feline immunodeficiency virus (FIV). Six specific pathogen-free, laboratory-housed cats were challenged intravenously with 1000 TCID₅₀ of the Maryland isolate of FIV (FIV-MD) at 8 months of age. The highest serum creatine kinase values were seen at 18 months postinfection (mean 9838, SD 4805 U/L) compared to preinfection (mean 950, SD 374 U/L). Needle EMG studies revealed abnormal spontaneous activity in 2 cats. All FIV-MD infected cats exhibited at least one abnormality in muscle pathology. Of the 24 muscle samples, 15 (63%) had histopathologic lesions. The predominant histologic abnormalities consisted of perivascular and pericapillary lymphocytic infiltration, and myofiber necrosis, phagocytosis, and regeneration. Lymphocytic infiltration was graded 2+ or higher in 12 of 24 muscle samples (0 = negligible; 4+ = extensive). Immunohistochemical phenotypic lymphocyte labeling in all cats demonstrated only CD8+ lymphocyte staining. This report demonstrates the presence of a FIV associated inflammatory myopathy in the adult cat. Several similarities are apparent in comparison to HIV-1 associated polymyositis reported in humans. Future studies in the cat may thus prove useful in elucidating the pathogenesis of retrovirus related myopathy in humans. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1680–1685, 1998     

Detection of varicella-zoster virus DNA by polymerase chain reaction in cerebrospinal fluid of patients with herpes zoster meningitis

Summary In three of five patients with herpes zoster meningitis, varicella-zoster virus (VZV) DNA was detected by the polymerase chain reaction (PCR) in the initial samples of cerebrospinal fluid. DNA fragments of group A or B, following classification of VZV strains by the size of the variable region IV of VZV genome, were found at the 7th, 10th and 24th illness day in the three positive cases: one of these cases did not have skin lesions. These results suggest that the detection of VZV DNA by PCR is useful for the diagnosis of herpes zoster meningitis, as well as for its molecular epidemiology.     

Mouse model of Bell's palsy induced by reactivation of herpes simplex virus type 1

In order to investigate the mechanism of Bell's palsy, we developed an animal model of facial nerve paralysis induced by the reactivation of herpes simplex virus type 1 (HSV-1). Eight weeks after recovery from facial nerve paralysis caused by inoculation with HSV-1, the mice were treated with auricular skin scratch at the site of the previous inoculation, or with intraperitoneal injection of anti-CD3 monoclonal antibody (mAb), or combination of both procedures. No mice developed facial nerve paralysis when they were treated with either auricular scratch or mAb injection alone. In contrast, 20% of mice developed facial nerve paralysis with the combined treatment. With one exception, no mouse treated with either auricular scratch or mAb injection showed HSV-I DNA in their facial nerve tissue, whereas 4 out of 6 mice receiving both treatments showed HSV-1 DNA on day 10 after treatment. Histopathological findings showed neuronal degeneration in the geniculate ganglion and demyelination of the facial motor nerve in paralyzed mice. These findings suggest that a combination of stimuli, local skin irritation, and general immunosuppression is essential for successfully inducing facial nerve paralysis in mice with latent HSV-1 infection.     

Rarity of JC virus DNA sequences and early proteins in human gliomas and medulloblastomas: the controversial role of JC virus in human neurooncogenesis

JC virus (JCV), the agent of progressive multifocal leucoencephalopathy (PML), exerts an oncogenic effect in several laboratory animal models. Moreover, JCV genomic DNA and early viral protein T-antigen have been detected in various types of human central nervous system (CNS) neoplasms. To further explore this association we have studied paraffin-embedded brain biopsy tissue from 60 neoplasms (55 gliomas and five medulloblastomas) and 15 reactive gliosis cases for the presence of JCV DNA sequences and proteins. Four post mortem cases of HIV-associated PML were used as positive controls. Samples were assessed by polymerase chain reaction (PCR) amplification of early (large T antigen) and late (virion protein 3) sequences and immunohistochemistry (IHC) with both PAb 2024 and anti-SV40 large T antigen monoclonal antibodies. Five cases (three neoplasms and two reactive gliosis instances) showed low viral DNA levels when PCR-tested for VP3 or large T, while no case was immunoreactive for any of the two antibodies used. The four PML cases yielded positive results with both PCR and IHC. Additionally, IHC with both antibodies was applied to a tissue micro-array including 109 CNS tumours and 21 reactive gliosis samples. No immunoreactivity was detected in any of these tissue micro-array samples. The rarity of JCV DNA sequences and early proteins in our brain tumours enriches the controversy over the role of JCV in human neurooncogenesis, whose clarification is in need of further molecular and epidemiologic studies.     

Localization of herpes simplex virus and varicella zoster virus DNA in human ganglia.

Human dorsal root ganglia from 14 randomly autopsied adults and 1 infant (all seropositive for both herpes simplex virus [HSV] and varicella zoster virus [VZV]) were examined for latent HSV-1 and VZV DNA by polymerase chain reaction. Thoracic ganglionic DNA from all subjects and trigeminal ganglionic DNA from 11 adults were analyzed. HSV-1 DNA was detected in trigeminal ganglia from 8 of 11 (73%) adults and in thoracic ganglia from 2 of 14 (14%) adults. VZV DNA was detected in trigeminal ganglia from 10 of 11 (91%) adults and in thoracic ganglia from 12 of 14 (86%) adults. None of the DNA samples were positive with primers specific for HSV-2. These findings indicate the presence of latent HSV-1 and VZV DNA in trigeminal ganglia and latent VZV DNA in thoracic ganglia of most seropositive adults. Furthermore, although HSV-1 latency most commonly develops in trigeminal ganglia, we also show for the first time the presence of HSV-1 latency in thoracic ganglia. Finally, both viruses can become latent in the same trigeminal ganglion.     

Spastic paraparesis associated with human T-lymphotropic virus type I: A clinical,serological, and genomic study in Iranian-born Mashhadi Jews

The Mashhadi-Jewish community originating in Iran is a closed and ethnically segregated population with a unique history and a high rate of intrafamilial marriage among its members. A high risk of infection by human T-lymphotropic virus type I (HTLV-I) and of adult T-cell leukemia associated with such infection was found in this population. HTLV-I is also associated with a syndrome of progressive spastic paraparesis. We therefore evaluated the occurrence of HTLV-I infection and spastic paraparesis in Mashhadi-born Iranian Jews who immigrated to Israel. We examined 83 Mashhadi-born subjects (52 women, 31 men; mean age, 61 ± 15.5 years) and 73 age-matched non-Mashhadi Iranian-born Jews. Blood samples were tested for HTLV-I antibodies by particle agglutination test. The polymerase chain reaction (PCR) was used to detect HTLV-I proviral DNA sequences from peripheral blood mononuclear cells. Fifteen Mashhadi-born Jews (18%) were both seropositive and PCR-positive for HTLV-I. Four HTLV-I-seronegative subjects were found to be positive for HTLV-I proviral DNA by PCR. Of the 19 HTLV-I–infected subjects (11 women, 8 men; mean age, 59 ± 16 years), 13 (68%) had spastic paraparesis of varying severity. There were no signs of myelopathy in the Mashhadi-born subjects who were negative for HTLV-I proviral DNA by PCR. None of the non-Mashhadi Iranian Jews was seropositive or PCR-positive for HTLV-I proviral DNA, or had clinical signs of spastic paraparesis. Our study indicates a high incidence of HTLV-I infection and spastic paraparesis in Mashhadi-born Iranian Jews. Possible transmission mechanisms may be related to a high rate of infection in this closed community, or to a genetically transmitted virus in a susceptible high-inbred population.     

聚合酶链反应（PCR）对单纯疱疹病毒性脑炎的临床诊断价值

应用聚合酶链反应（ＰＣＲ）检测技术对１１８例颅内感染性疾病患者及３７例无神神经系统疾病患者脑脊液（ＣＳＦ）中的单纯疱疹病毒ＤＮＡ（ＨＳＶ－ＤＮＡ）进行了检测及分型。结果提示：“散发性脑炎”组的阳性率为３８．４６％（２０／５２），细菌、真菌性脑膜炎、其它病毒性脑炎组以及无神经系统疾病组均为阴性。作者认为：①本检测是目前单纯疹病毒性脑炎（ＨＳＥ）较为简便而准确的早期诊断方法之一；②ＨＳＶ分型检测，对病原诊断更具有全面性；③两型单纯疱疹病毒均可引起ＨＳＥ。     

Failure to detect viral genomic sequences of three viruses (herpes simplex, simian virus 40 and adenovirus) in human and rat brain tumors

Little is known about oncogenesis in brain tumors. Viruses are thought to be involved in some neurological diseases, the presence of subfractions of viral DNA has been reportedin various circumstances and the oncogenicity of some viruses has been demonstrated in animal experiments. The discovery of homologies between retroviral ancogenes and normal cellular genes (proto-oncogenes) has stimulated once again the search for viral responsability in oncogenesis. Having a large bank of tumor material available, we systematically examined 39 brain tumors usign Southern blot hybridization with DNAs of three viruses, known to be involved in neurological diseases: herpes simplex virus (HSV), simian virus 40 (SV40) and adenovirus type 2 (Ad 2). We detected no homology between the DNAs of the examined material and the viral DNA probes. We compare these negative results with those of other published studies and discuss the experimental conditions, with special reference to the possibility of non-specific hybridization, which could account for the positive results reported. The present negative results could be interpreted either as absence of involvement of the three investigated viruse in brain tumor oncogenesis, or an indirect involvement through a hit-and-run mechanism or a highly dispersed state of the viral sequences among the host genome, which would prevent hybridization with the probe, as it has been supposed to be the case during the latency phase of herpes virus.

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Sommario Poco si sa su oncogenesi dei tumori cerebrali. Si pensa che i virus siano coinvolti in alcune malattie neurologiche e la presenza di sottofrazioni di DNA virale è stata riportata in varie cirkostanze e l'oncogenicità di alcuni virus è stata dimostrata in animali da esperimento. Inoltre la scoperta di omologia tra gli oncogeni retrovirali e i normali geni cellulari ha stimolato la ricerca sulla responsabilità virale dell'oncogenesi. Gli Autori hanno sistematicamente esaminato 39 tumori cerebrali usando la ibridizzazione con DNA di 3 virus coinvolti in malattie neurologiche: quello dell'herpes simplex (HSV), il virus 40 (SV40) e l'adenovirus tipo 2 (Ad2). Non si è trovata omologia tra i DNA del materiale esaminato e il DNA virale. Sono stati allora comparati questi risultati negativi con quelli positivi di altri Autori riferendosi soprattutto alla possibilità di una ibridizzazione non specifica che può giustificare i risultati positivi riportati. Questa ricerca negativa può essere interpretata sia come un'assenza di coinvolgimento dei tre virus investigati nella oncogenesi dei tumori cerebrali, sia come espressione di una disposizione delle sequenze virali nel genoma ospite con conseguente prevenzione della ibridizzazione, come è stato supposto avvenga durante le fasi di latenza del virus herpetico.

     

Low prevalence of human herpesvirus-6 and varicella zoster virus in blood of multiple sclerosis patients,irrespective of inflammatory status or disease progression

Herpesviruses, including human herpesvirus-6 and varicella zoster virus, have been implicated in the disease aetiology of multiple sclerosis. These viruses are capable of reactivation, reminiscent of the relapsing-remitting nature of multiple sclerosis. However, viral DNA has also been reported present in healthy controls, often at similar prevalence rates. This study aimed to determine whether prevalence could be associated with different stages of activity of the disease as well as the inflammatory status of the patients. Polymerase chain reaction assays were used to screen for human herpesvirus-6 and varicella zoster virus DNA in blood from 31 Caucasian patients with multiple sclerosis and 30 healthy age, sex and race matched control subjects. The patients were screened for inflammation using C-reactive protein as a marker and were also categorized according to their remitting/relapsing status. Results were positive for human herpesvirus-6 in blood from only one patient (3.2%) and human herpesvirus-6 DNA was not present in any control subjects. Varicella zoster virus was not detected in either the patients or control subjects. Similar to some other studies we saw an absence or very low viral positivity in blood from both patients and controls. These findings were irrespective of relapse episodes, increased inflammatory status or duration of the disease. Results therefore do not support a causative role for either human herpesvirus-6 or varicella zoster virus in the disease aetiology of multiple sclerosis, but rather that prevalence in patients may be linked to that of the general population.     

JC virus DNA in cerebrospinal fluid of human immunodeficiency virus—infected patients: Predictive value for progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a lytic infection of oligodendrocytes by the human papovavirus JC. Patients with defects in cell-mediated immunity are at risk for active disease: a usually lethal demyelination of the brain. PML develops in at least 4% of patients with the acquired immunodeficiency syndrome (AIDS). Definitive diagnosis currently requires brain biopsy. Previous attempts to detect JC virus DNA by polymerase chain reaction in cerebrospinal fluid of PML patients, particularly those with human immunodeficiency virus type 1 (HIV - 1) infection, have been of low sensitivity. In the present study, cerebrospinal fluid was assayed by polymerase chain reaction from 26 HIV-1-positive patients with PML, 114 HIV-1-positive control subjects, and 16 control subjects who were HIVv1 negative or were without risk factors for HIV disease. Polymerase chain reaction conditions were optimized to detect a single copy of viral DNA in 50 μl of cerebrospinal fluid. Specificity of the polymerase chain reaction product was confirmed by size on gel electrophoresis and Southern blot hybridization. JC virus DNA was detected in 24 of 26 samples from patients with PML: 8 of 8 with tissue diagnosis and 16 of 18 with strong clinical and magnetic resonance imaging evidence of PML. Among control subjects, 11 of 130 samples were positive for JC virus: 10 of 114 samples from HIV-infected patients and one from an HIVvnegative patient with risk factors for PML and an unexplained hemiparesis. Overall senstivity was 92% (24/26); specificity was, at minimum, 92% (119/130). Treatments for PML are now in clinical trials. This assay provides a safe, inexpensive means of establishing the diagnosis of a potentially treatable condition. Furthermore, our data suggest that a subgroup of presymptomatic patients who may be at high risk for PML can be identified. Such patients may be particularly suitable for prophylactic interventions.     

肾移植术后受者BK病毒血症的高危因素分析

背景：肾脏移植的受者BK病毒感染相关性肾病可引起移植肾功能不全和输尿管梗阻，是移植肾失功的重要原因之一。 目的：检测肾移植患者后BK病毒血症的发生率，分析BK病毒感染的危险因素。 设计、时间及地点：回顾性病例分析，于2001-09/2007-12首都医科大学附属北京友谊医院泌尿外科完成。 对象：因终末期肾病而进行同种异体肾移植患者121例，同时选取20例因肾功能衰竭患者而行规律血液透析患者作为对照组。 方法：应用荧光实时定量PCR检测121例肾移植患者移植后不同时期血液标本中BK病毒 DNA含量；并根据检测结果进行分为血液BK病毒 DNA均阳性组和血液BK病毒 DNA阴性组。比较两组患者性别、年龄、供肾冷缺血时间，是否发生急性排斥反应、是否发生移植肾功能延迟恢复、免疫抑制剂方案和供肾类型的差异。 主要观察指标：应用logistic多因素分析，确定BK病毒血症发生的危险因素。 结果：肾移植受者BK病毒病毒血症的发生率为24.7%(30/121)，高于肾功能衰竭血透患者其阳性率为5%(1/20)，差异有显著性意义(P=0.03)。多因素分析显示冷缺血时间3.34 (RR 3.34，95% CI 2.76~5.60)和无心跳供肾(RR 2.19，95% CI 1.32~3.97)是移植术后BK病毒血症的危险因素。而移植前年龄、标本留取时间和激素冲击治疗与移植后受者BK病毒血症发生无关。 结论：肾移植后BK病毒感染发生率增高，冷缺血时间延长和无心跳供肾为肾移植后BK病毒感染高危因素。     

Demonstration of herpes simplex virus DNA in CSF cells by in situ hybridization for early diagnosis of herpes encephalitis

Summary Herpes simplex virus (HSV) was studied by in situ DNA hybridization with a biotinylated cDNA probe in 56 air-dried methanol-fixed cerebrospinal fluid (CSF) cell preparations which had been collected from 12 patients with herpes simplex encephalitis (HSE) during the previous 5 years. In three additional HSE cases, freshly prepared acetone-fixed CSF cell preparations were available. In all cases, CSF cell preparations were obtained by cytocentrifugation. Herpes simplex virus DNA could be demonstrated in 8 of the 12 HSE cases with methanol-fixed cells (66%) and in all 3 cases with fresh acetone-fixed CSF cells. The earliest CSF sample was available at the onset of symptoms and showed positive DNA hybridization. In three cases hybridization was positive after a clinical course of more than 5 weeks but was usually found in the 1st week of illness before the beginning of specific inthrathecal IgG synthesis. In 54 control cases with other acute inflammatory diseases of the CNS, including 14 cases of varicella-zoster meningitis, no positive hybridization was detected. These findings strongly suggest that in situ hybridization in CSF cells is a reliable tool for the early and rapid diagnosis of HSE, especially at the onset of the disease, when no antibodies can be detected.     

Absent anti-N-methyl-D-aspartate receptor NR1a antibodies in herpes simplex virus encephalitis and varicella zoster virus infections

Purpose: A 2012 report and subsequent case series described anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in patients during the acute phase and relapse of herpes simplex virus 1 (HSV1) encephalitis (HSV1E). However, the prevalence of this phenomenon is unknown and systematic studies on other viral infections of the nervous system are missing. Materials and methods: We retrospectively analyzed serial cerebrospinal fluid (CSF) and serum samples of consecutive patients treated for neurological HSV1, HSV2 and varicella zoster virus (VZV) infections in our tertiary care university hospital between 2003 and 2013 for the presence of antibodies directed against the NR1a subunit of the NMDAR using indirect immunofluorescence. Results: In total, 88 patients with the following infections were identified through an electronic database search: HSV1 (24 with encephalitis), HSV2 (6 with meningitis, 3 with encephalitis and 1 with myelitis), or VZV (3 with meningitis, 33 with encephalitis, 17 with radiculitis and 1 with myelitis). Two patients with HSV1E and HSV2E, respectively, experienced a clinical relapse. Clinical follow-up was for up to 85 months, and repetitive serum and CSF analyses for up to 43 months. However, at no time did any of the 88 patients exhibit anti-NMDAR NR1a antibodies. Conclusions: In this study, we did not detect anti-NMDAR NR1a antibodies in serial CSF and serum samples of HSV1E patients or patients with other viral infections (HSV2 and VZV). However, the presence of antibodies directed against other epitopes of the NMDAR and other neuronal cell surface antigens cannot be excluded, necessitating further studies.     

Varicella-zoster virus at relapses of multiple sclerosis

Abstract The possible participation of different herpes viruses was studied during exacerbations of multiple sclerosis (MS). We searched for the presence of DNA from the following herpes viruses: varicella zoster virus (VZV), herpes-simplex viruses 1 and 2; Epstein-Barr virus (EBV) and human herpes-virus-6 (HHV6) in mononuclear cells from patients with MS during relapse (n = 40), MS during remission (n = 131) and controls (n = 125). Additionally, immune cells containing viral antigens were quantified by flow cytometry, and VZV load was determined by real time PCR in 2 MS patients at various times during relapse and remission. DNA from VZV was found in 95% of MS patients during relapse and in 17% during remission; all controls were negative; by contrast, DNA from HHV6 was found in 24% of MS patients during relapse and in 2% during remission; DNA from herpes simplex viruses was not found in any subject; and DNA from EBV was found in a similar percentage of subjects from all groups. Sequential quantification of VZV-load showed a curve that increased during relapse and disappeared at remission. Also, VZV antigens were found inside a large number of immune cells from MS patients during relapse as compared with MS patients on remission and controls. In the typical forms of VZV infection, varicella and herpes-zoster, DNA from VZV is found in mononuclear cells exclusively during brief periods at the beginning of the active infection, but not during latency; thus, the conspicuous presence of VZV during relapses of MS may indicate a period of active infection and suggests the participation of VZV in the pathogenesis of MS.     

巢式聚合酶链反应检测脑脊液中单纯疱疹病毒DNA

应用巢式聚合酶链反应(PCR)检测患者脑脊液(CSF)中单纯疱疹病毒1型(HSV-1)DNA。23例经鞘内HSV-1特异性IgG抗体检测阳性的“HSV-1型性脑炎(HSE)”中19例PCR阳性,4例阴性患者病程均超过1个月。22例IgG阴性的“散发性脑炎”中7例PCR阳性,此7例皆于发病1周内检查CSF,其中2例取材于发病当日。1周后复查7例患者,CSF PCR仍为阳性,IgG皆阴性,提示PCR适用于HSE的早期诊断。     

Herpes simplex virus type 2 DNA detected in cerebrospinal fluid of 9 patients with Mollaret's meningitis

We present clinical and virological data on 9 patients, 7 women and 2 men aged 31–56 years, with recurrent aseptic meningitis (Mollaret's meningitis). Polymerase chain reaction detected Herpes simplex virus type 2 DNA in cerebrospinal fluid samples from all patients collected during their latest attacks of meningitis. Six patients had no history of genital herpes. Only 1 patient was offered prophylactic antiviral treatment during the study period (45 months).     

Neuropathology of human T lymphotropic virus type I-associated myelopathy

In order to clarify pathogenesis of human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) a detailed neuropathological analysis of eight autopsy patients with HAM/TSP was performed. Inflammatory infiltrates of mononuclear cells and degeneration of myelin and axons were noted in the middle to lower thoracic spinal cords and were extended continuously to the entire spinal cord. Horizontal distribution of inflammatory lesions was symmetric at any spinal levels. Immunohistochemical analysis demonstrated T cell dominance. The numbers of CD4+ T cells and CD8+ T cells were present in equal numbers in patients with shorter clinical course. Apoptosis of helper/inducer T cells were observed in the presence of TIA1+ cytotoxic T cells in these active inflammatory lesions. Inflammatory infiltrates were markedly decreased and CD8+/TIA1- T cells were predominated over CD4+ cells in patients with prolonged clinical course. HTLV-I proviral deoxyribonucleic acid (DNA) amounts in the freshly frozen spinal cord measured by quantitative polymerase chain reaction (PCR) were well correlated with the numbers of infiltrated CD4+ cells. In situ PCR of HTLV-I provial DNA using multi-primar pairs demonstrated the presence of HTLV-I infected cells exclusively in the mononuclear infiltrates of perivascular areas. From these findings, it is suggested that the target of the inflammatory process seen in HAM/TSP lesions may be HTLV-I infected CD4+ T cells infiltrating the spinal cord.