Meningoencephalitis caused by human herpesvirus-6 in an immunocompetent adult patient: Case report and review of the literature

Summary Human herpesvirus-6 (HHV-6) is the etiologic agent of roseola infantum, and has been implicated as a possible cause of encephalitis in pediatric and adult patients. A case of meningoencephalitis in an otherwise healthy, immunocompetent 59-year-old woman is described. The diagnosis of HHV-6 meningoencephalitis was confirmed by detecting viral DNA in cerebrospinal fluid collected in the acute stage of the disease by polymerase chain reaction. The patient was treated with acyclovir and recovered without any sequelae. The current knowledge of the pathophysiology, clinical course and outcome of HHV-6 meningoencephalitis in immunocompetent adult patients is also reviewed.     

Comprehensive investigation of the presence of JC virus in AIDS patients with and without progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML), a viral-induced demyelinating disease, is becoming relatively common, while many diagnostic and pathogenetic aspects remain to be clarified. A study was therefore undertaken in 64 AIDS patients suffering from various neurological disorders, including PML (12 subjects), with the specific objective of searching for JC virus (JCV) DNA by nested PCR (n-PCR) in cerebrospinal fluid (CSF), peripheral blood mononuclear cells (PBMCs), and urine collected from all patients. CSF examination, CD4 and CD8 counts, neurological examinations, and neuroradiological investigations were undertaken. JCV DNA was detected in 92% of CSF specimens in 75% of the PBMCs and urine samples from the PML patients, whereas among the non-PML patients JCV DNA was not detected in any CSF samples, but was found in 10% of PBMCs and in 39% of the urine specimens. BKV and JCV DNA viruria was observed simultaneously in 6% of the AIDS patients without PML. The routine CSF tests including IgG oligoclonal bands, the Link, and Tourtellotte IgG indexes, did not show a typical pattern in PML cases. The data obtained clearly indicate that the detection of JCV DNA in CSF constitutes an efficient marker for PML diagnosis. The simultaneous presence of JCV DNA in the CSF, PBMCs, and urine samples from the PML patients, who did not differ from controls with regard to their immunosuppressive status, suggests that JCV could be carried into the central nervous system (CNS) by infected PBMCs. J. Med. Virol. 52:235–242, 1997. © 1997 Wiley-Liss, Inc.     

Detection and typing of JC virus in autopsy brains and extraneural organs of AIDS patients and non-immunocompromised individuals.

The distribution of JC virus (JCV) variants in the brain, lung, liver, kidney, spleen and lymph nodes collected at autopsy from AIDS patients with (Group A: 10 Ss) and without (Group B: 5 Ss) progressive multifocal leukoencephalopathy (PML) and from HIV-negative patients (Group C: 5 Ss), was examined by amplifying the JCV large T antigen (LT), the regulatory (R) and the VP1 regions. Among the samples from the PML patients, JCV DNA was detected in all of the demyelinating areas, in 60% of the lesion-free brain tissues, in 60% of the lung tissues and in 40% of the spleen and kidney tissues, whereas all liver and lymph node sections were negative. JCV DNA was also found in two of the five brain specimens, in two of the five kidney specimens, in one of the five lung specimens from the HIV-positive patients without PML and in the brain specimens from two of the five HIV-negative subjects. Nucleotide sequence analysis indicated that all of the R region amplified from extraneural tissues had rearrangements similar to those of the Mad-4 strain and that VP1-region amplified products were similar to the Mad-1 strain. In the brain specimens from two PML patients, we found a unique rearranged R region, along with a VP1 region of JCV type 2. In addition, an almost unique variant with multiple rearrangements in the R region and unusual base mutations in the VP1 region was detected in the brain sample from another PML patient. The data indicate that diffuse visceral involvement of JCV is particularly frequent in AIDS patients with PML. Moreover, the presence of rearrangements and mutations, involving different regions of the viral genome, observed in PML-affected brain tissues, could represent a risk factor for the development of PML in immunosuppressed individuals.     

Molecular characterization and sequence analysis of polyomavirus strains isolated from needle biopsy specimens of kidney allograft recipients

We retrospectively examined 29 renal allograft biopsy specimens from 42 kidney transplant recipients by means of molecular biologic techniques (nested polymerase chain reaction), immunohistochemical analysis (anti-SV40 antibody), and histologic examination to evaluate the presence of polyomaviruses (PVs), viral genotypes, genomic mutations, and their pathologic significance. PV genomes were found in six cases (21%); restriction fragment length polymorphism analysis characterized 4 as JC virus (JCV) and 2 as BK virus (BKV). The latter also were positively stained immunohistochemically and showed histologically typical intranuclear viral inclusions; JCV cases were negative. DNA sequence analysis revealed only minor changes in the 4 JCV cases (3 archetypes and 1 JCV type 3, not associated with a known pathogenic genotype) but identified 2 specific variants in the BKV isolates (AS and WW strains). Given the different histologic findings (mixed inflammatory infiltration in the AS and no inflammation in the WW strain), we speculate that different BKV strains may cause differential damage in transplanted kidneys. Finally, the negative histologic and immunohistochemical JCV results, as well as the absence of viral mutations, indicate that JCV renal infection is latent in transplant recipients.     

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.     

PCR detection of JC virus DNA in brain tissue from patients with and without progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system, which is thought to be a result of the reactivation of JC virus (JCV), a human polyomavirus. The disease occurs in individuals with immunosuppression and in recent years there has been an increase in PML cases due to AIDS. A nested polymerase chain reaction (n-PCR) was employed to detect JCV and BK virus (BKV) DNA in brain tissue collected postmortem from 28 AIDS patients with PML and from 13 patients without PML, but with other diagnoses, including solid tumors, Alzheimer's disease, thromboembolism, myocardial infarction and acute cerebrovascular diseases. All 28 brain specimens from the patients with PML were positive for JCV DNA when tested by n-PCR and three of the latter were also positive for BKV DNA. These results were confirmed by an enzyme restriction analysis and a DNA hybridization assay. Interestingly, in this study, JCV DNA was also found in 6 brain tissue specimens from 4 subjects with diseases unrelated to PML or AIDS. All the brain specimens from the control group were negative for BKV DNA. The results confirm that the n-PCR is a useful tool for PML diagnosis. The presence of JCV DNA in the brain tissue of patients without PML is particularly important since it indicates that JCV could be latent in the brains of immunocompetent individuals. Moreover, detection of simultaneous presence of JCV and BKV in the brain tissue of the patients with PML demonstrates that BKV may also infect the human brain without causing any apparent neurological disease. © Wiley-Liss, Inc.     

Expression of the urokinase plasminogen activator receptor (uPAR) and its ligand (uPA) in brain tissues of human immunodeficiency virus patients with opportunistic cerebral diseases

The urokinase plasminogen activator receptor (uPAR) and its ligand (uPA) play an important role in cell migration and extracellular proteolysis. We previously described uPAR/uPA overexpression in the cerebrospinal fluid (CSF) and brain tissues of patients with human immunodeficiency virus (HIV)-related cerebral diseases. In this study, we examined uPAR/uPA expression by immunohistochemistry (IHC) in brains of HIV patients with opportunistic cerebral lesions and in HIV-positive/negative controls. uPAR was found in macrophages/microglia with the highest levels in cytomegalo-virus (CMV) encephalitis, toxoplasmosis, and lymphomas; in cryptococcosis and progressive multifocal leukoencephalopathy (PML) cases, only a few positive cells were found and no positivity was observed in controls. uPA expression was demonstrated only in a few macrophages/microglia and lymphocytes in all the cases and HIV-positive controls without different pattern of distribution; no uPA immunostaining was found in cryptococcosis and HIV-negative controls. The higher expression of uPAR/uPA in most of the opportunistic cerebral lesions supports their role in these diseases, suggesting their contribution to tissue injury.