Recovery of a neurovirulent human coronavirus OC43 from an infectious cDNA clone.
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This study describes the assembly of a full-length cDNA clone of human coronavirus (HCoV)-OC43 in a bacterial artificial chromosome (BAC). The BAC containing the full-length infectious cDNA (pBAC-OC43(FL)) was assembled using a two-part strategy. The first step consisted in the introduction of each end of the viral genome into the BAC with accessory sequences allowing proper transcription. The second step consisted in the insertion of the whole HCoV-OC43 cDNA genome into the BAC. To produce recombinant viral particles, pBAC-OC43(FL) was transfected into BHK-21 cells. Recombinant virus displayed the same phenotypic properties as the wild-type virus, including infectious virus titers produced in cell culture and neurovirulence in mice. (+info)
Influence of pseudorabies virus proteins on neuroinvasion and neurovirulence in mice.
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Neurotropism is a distinctive feature of members of the Alphaherpesvirinae. However, its molecular basis remains enigmatic. In the past, research has been focused mainly on the role of viral envelope proteins in modulating herpesvirus neuroinvasion and neurovirulence (T. C. Mettenleiter, Virus Res. 92:192-206, 2003). To further analyze the molecular requirements for neuroinvasion of the alphaherpesvirus pseudorabies virus (PrV), adult mice were infected intranasally with a set of single- or multiple-deletion mutants lacking the UL3, UL4, UL7, UL11, UL13, UL16, UL17, UL21, UL31, UL34, UL37, UL41, UL43, UL46, UL47, UL48, UL51, US3, US9, glycoprotein E (gE), gM, UL11/US9, UL11/UL16, UL16/UL21, UL11/UL16/UL21, UL11/gE, UL11/gM, UL43/gK, UL43/gM, or UL43/gK/gM genes. Neurovirulence was evaluated by measuring mean survival times compared to that after wild-type virus infection. Furthermore, by immunohistochemical detection of infected neurons, the kinetics of viral spread in the murine central nervous system was investigated. (+info)
Human immunodeficiency virus and the central nervous system.
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The pandemic of HIV/AIDS continues to grow daily. Incident cases among women, intravenous drug users and ethnic minorities comprise the fastest growing segment of the HIV-infected population, and the number of HIV-infected individuals over the age of 50 is growing rapidly. Today, the central nervous system and the immune system are seen as main targets of HIV infection. Significant progress in the knowledge and treatment of AIDS has been obtained in recent years. The neurological manifestations directly related to HIV are acute viral meningitis, chronic meningitis, HIV-associated dementia (HAD), vacuolar myelopathy, and involvement of the peripheral nervous system. (+info)
High pathogenicity of wild-type measles virus infection in CD150 (SLAM) transgenic mice.
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Measles virus (MV) infection causes an acute childhood disease, associated in certain cases with infection of the central nervous system and development of a severe neurological disease. We have generated transgenic mice ubiquitously expressing the human protein SLAM (signaling lymphocytic activation molecule), or CD150, recently identified as an MV receptor. In contrast to all other MV receptor transgenic models described so far, in these mice infection with wild-type MV strains is highly pathogenic. Intranasal infection of SLAM transgenic suckling mice leads to MV spread to different organs and the development of an acute neurological syndrome, characterized by lethargy, seizures, ataxia, weight loss, and death within 3 weeks. In addition, in this model, vaccine and wild-type MV strains can be distinguished by virulence. Furthermore, intracranial MV infection of adult transgenic mice generates a subclinical infection associated with a high titer of MV-specific antibodies in the serum. Finally, to analyze new antimeasles therapeutic approaches, we created a recombinant soluble form of SLAM and demonstrated its important antiviral activity both in vitro and in vivo. Taken together, our results show the high susceptibility of SLAM transgenic mice to MV-induced neurological disease and open new perspectives for the analysis of the implication of SLAM in the neuropathogenicity of other morbilliviruses, which also use this molecule as a receptor. Moreover, this transgenic model, in allowing a simple readout of the efficacy of an antiviral treatment, provides unique experimental means to test novel anti-MV preventive and therapeutic strategies. (+info)
Polymerase chain reaction analysis and oligoclonal antibody in the cerebrospinal fluid from 34 patients with varicella-zoster virus infection of the nervous system.
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OBJECTIVE: To study cerebrospinal fluid (CSF) and serum samples from 34 consecutive patients suspected of having varicella-zoster virus (VZV) infection of the central nervous system (CNS). POPULATION AND METHODS: The patients were divided into three groups. The first group consisted of 27 patients with a rash in one to three dermatomes and clinical suspicion of meningitis and radiculitis; among them, three subgroups were distinguished according to the affected dermatome: ophthalmicus (n = 9), oticus (n = 11) and cervico-thoraco-lumbar zoster (n = 7). Four cases of zoster sine herpete (ZSH) were included in the second group: these patients presented with either radiculitis (n = 2) or meningoencephalitis (n = 2), without cutaneous eruption. The third group consisted of three patients with a generalised rash and encephalitis. A polymerase chain reaction (PCR) for VZV DNA and antigen-driven immunoblots for oligoclonal anti-VZV antibodies were carried out on all CSF samples. RESULTS: PCR of the CSF was positive in 44% of the patients from the first group, mainly within the first 7 days after eruption. In addition, intrathecal synthesis of anti-VZV antibodies was detected in 37% of patients, always after an interval of 7 days (p<0.0001). Among the four patients with ZSH, a positive VZV PCR was detected in three patients and CSF-specific oligoclonal anti-VZV antibodies in two. PCR was also positive in the CSF of two of the three patients with generalised rash and encephalitis; local production of anti-VZV antibodies was seen in a second CSF sample in one patient, and was also present in the third patient. CONCLUSION: Amplification of VZV DNA by PCR in the CSF and antigen-driven immunoblots have important diagnostic value in suspected VZV infection, although their presence depends on the timing of the CSF sampling. VZV is thought to be a causative agent in unexplained cases of meningitis associated with radiculitis or focal CNS symptoms, even in the absence of skin manifestations. In such patients, rapid diagnosis by this combined approach permits early antiviral treatment. (+info)
HIV pharmacology: barriers to the eradication of HIV from the CNS.
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Total eradication of HIV-1 is not yet achievable, in part because reservoirs of latent HIV-1 can develop within lymphoid tissue, the testes, and the central nervous system (CNS). The presence of HIV-1 in the CNS is clinically significant because of its association with the development of HIV dementia, which occurs in up to one fifth of untreated patients. This review summarizes current theory regarding HIV-1 infection within the CNS, describes physiologic and pharmacologic factors limiting CNS penetration of antiretroviral drugs used to treat HIV-1 infection, and reviews current treatment of CNS HIV-1 infection and HIV encephalopathy. (+info)
Trends in encephalitis-associated deaths in the United States.
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The United States national mortality statistics and HIV/AIDS surveillance data were analysed to determine trends in encephalitis-associated deaths and to assess the impact of HIV infection on those deaths during 1979-1998, a period when ICD-9 codes were used for coding deaths in the United States. A total of 25125 encephalitis deaths were reported; 4779 of them (19%) had concurrent HIV infection. Overall encephalitis death rates remained stable, but they increased for groups where HIV infection was common and declined or remained unchanged for others. For persons without HIV infection, the rates declined in all demographic groups. Encephalitis deaths in HIV-infected persons followed general trends for HIV deaths in the United States. The rates in the HIV-infected population were several hundred- to thousand-fold higher than in the HIV-uninfected population. HIV infection was largely responsible for the lack of overall decline in the considerable mortality associated with encephalitis in the United States during 1979-1998. (+info)
Invader plus method detects herpes simplex virus in cerebrospinal fluid and simultaneously differentiates types 1 and 2.
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We report here on the development and validation of a prototype Invader Plus method for the qualitative detection of herpes simplex virus types 1 and 2 in cerebrospinal fluid (CSF). The method combines PCR and Invader techniques in a single, closed-tube, continuous-reaction format that gives an analytical sensitivity of approximately 10 copies per reaction. The clinical sensitivity and specificity were 100.0% and 98.6%, respectively, when the results of the method were validated against the results obtained with a PCR colorimetric microtiter plate system by use of clinical CSF specimens. (+info)