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Furious and paralytic rabies of canine origin: neuroimaging with virological and cytokine studies.

Laothamatas J, Wacharapluesadee S, Lumlertdacha B, Ampawong S, Tepsumethanon V, Shuangshoti S, Phumesin P, Asavaphatiboon S, Worapruekjaru L, Avihingsanon Y, Israsena N, Lafon M, Wilde H, Hemachudha T

Department of Radiology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Furious and paralytic rabies differ in clinical manifestations and survival periods. The authors studied magnetic resonance imaging (MRI) and cytokine and virus distribution in rabies-infected dogs of both clinical types. MRI examination of the brain and upper spinal cord was performed in two furious and two paralytic dogs during the early clinical stage. Rabies viral nucleoprotein RNA and 18 cytokine mRNAs at 12 different brain regions were studied. Rabies viral RNA was examined in four furious and four paralytic dogs during the early stage, and in one each during the late stage. Cytokine mRNAs were examined in two furious and two paralytic dogs during the early stage and in one each during the late stage. Larger quantities of rabies viral RNA were found in the brains of furious than in paralytic dogs. Interleukin-1beta and interferon-gamma mRNAs were found exclusively in the brains of paralytic dogs during the early stage. Abnormal hypersignal T2 changes were found at hippocampus, hypothalamus, brainstem, and spinal cord of paralytic dogs. More widespread changes of less intensity were seen in furious dog brains. During the late stage of infection, brains from furious and paralytic rabid dogs were similarly infected and there were less detectable cytokine mRNAs. These results suggest that the early stage of furious dog rabies is characterized by a moderate inflammation (as indicated by MRI lesions and brain cytokine detection) and a severe virus neuroinvasiveness. Paralytic rabies is characterized by delayed viral neuroinvasion and a more intense inflammation than furious rabies. Dogs may be a good model for study of the host inflammatory responses that may modulate rabies virus neuroinvasiveness.

Published 29 April 2008 in J Neurovirol, 14(2): 119-29.
Full-text of this article is available online (may require subscription).


Articles on Virology published 28 April 2008:

Immunologic, Virologic, and Clinical Consequences of Episodes of Transient Viremia During Suppressive Combination Antiretroviral Therapy.   J Acquir Immune Defic Syndr, 48(1): 104-108.

OBJECTIVE:: To investigate immunologic, virologic, and clinical consequences of episodes of transient viremia in patients with sustained virologic suppression. METHODS:: From the AIDS Therapy Evaluation Project, Netherlands cohort, 4447 previously therapy-naive patients were selected who were on continuous combination antiretroviral therapy and had initial success (2 consecutive HIV RNA measurements <50 copies/mL). During episodes of viral suppression (RNA <50 copies/mL), low-level ... [Abstract] [Full-text]

Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses.   Blood, 111(9): 4660-3.

Macrophages are reservoirs of HIV-1 infection, proposed to transmit virus to CD4(+) T cells, the primary target of the virus. Here we report that human monocyte-derived macrophages (MDMs) rapidly spread HIV-1 to autologous CD4(+) T cells resulting in productive infection. Transmission takes place across transient adhesive contacts between T cells and MDMs, which have the features of a virological synapse including copolarization of CD4 on the T cell with HIV-1 Gag and Env on the macrophage. We ... [Abstract] [Full-text]


Articles on Virology published 22 April 2008:

Insulin resistance impairs rapid virologic response in HIV/hepatitis C virus coinfected patients on peginterferon-alfa-2a.   AIDS, 22(7): 857-61.

OBJECTIVES: To investigate the association between insulin resistance and rapid virologic response. DESIGN: All consecutive HIV/hepatitis C virus coinfected patients who started peg-interferon alpha-2a (180 microg/week) and ribavirin 1000-1200 mg/day were analysed. METHODS: Insulin resistance was defined according to the homeostasis model of assessment-insulin resistance calculated as fasting insulin (mIU/l) x fasting glucose (mmol/l)/22.5. Rapid virologic response was defined as testing ... [Abstract] [Full-text]


Articles on Virology published 21 April 2008:

Cyclin-dependent kinase 9: a key transcriptional regulator and potential drug target in oncology, virology and cardiology.   Trends Pharmacol Sci.

Unlike other CDKs, CDK9 does not regulate the cell cycle but promotes RNA synthesis in genetic programmes for cell growth, differentiation and viral pathogenesis. It is becoming clear that CDK9 inhibition contributes to the anticancer activity of most CDK inhibitors under clinic investigation. CDK9 was discovered in the context of HIV research because retroviruses hijack host transcription and CDK9 inhibitors might become specific antiretroviral agents, particularly as they might prevent drug ... [Abstract] [Full-text]

Virological and Immunological Correlates of Mother-to-Child Transmission of Cytomegalovirus in The Gambia.   J Infect Dis, 197(9): 1307-14.

Background. @nbsp; Cytomegalovirus (CMV) is the most common congenital infection and can follow primary and recurrent maternal infection. We studied correlates of vertical transmission of CMV in The Gambia, where most children acquire CMV during the first year of life. Methods. @nbsp; A cohort of 281 mothers and infants was recruited at birth. Infants were prospectively followed up for CMV infection during the first year of life. Excretion of CMV and antiviral immune response were studied at ... [Abstract] [Full-text]


Articles on Virology published 17 April 2008:

Associations between the human MHC and sustained virologic response in the treatment of chronic hepatitis C virus infection.   Genes Immun.

The human major histocompatability complex (MHC) genes encode the human leukocyte antigens, which are important in antigen presentation and regulation of CD8+ and CD4+ T cells. Response to therapies in hepatitis C virus (HCV) infection is highly variable (30-80%) and lower response rates have been reported among African Americans (AA; approximately 30%) compared to Caucasian Americans (CA; approximately 50%) infected with genotype-1 viruses. We evaluated whether MHC gene variants were ... [Abstract] [Full-text]


Articles on Virology published 10 April 2008:

Lopinavir/ritonavir monotherapy as maintenance treatment in HIV-infected individuals with virological suppression: results from a pilot study in Brazil.   HIV Med, 9(5): 270-6.

Objective The aim of the study was to evaluate the possibility of using lopinavir/ritonavir (LPV/RTV) alone as maintenance therapy in HIV-infected individuals with virological suppression. Design This was a single-armed single-centre pilot trial. Methods Asymptomatic HIV-infected patients on highly active antiretroviral therapy (HAART) including LPV/RTV, and with plasma HIV RNA <40 copies/mL for at least 6 months, were enrolled in the study, during which they continued with LPV/RTV alone. ... [Abstract] [Full-text]


Articles on Virology published 9 April 2008:

Evaluation of initial virological response to adefovir and development of adefovir-resistant mutations in patients with chronic hepatitis B.   J Viral Hepat, 15(5): 392-8.

The aims of the present study were to assess initial virological response (IVR) to adefovir (ADV) treatment for chronic hepatitis B, to identify patients with suboptimal response and to determine the incidence of ADV-resistant mutants. All patients treated with ADV for at least 12 months were evaluated for virological response and ADV resistance. IVR was defined as a reduction > or = 4 log10 IU/mL in hepatitis B virus (HBV)-DNA at month 6. Forty-two patients were analysed. Mean treatment ... [Abstract] [Full-text]


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