Disease Virus Infection in Animals and Humans
Jürgen A. Richt,* Isolde Pfeuffer,* Matthias Christ,* Knut Frese,†Karl Bechter,‡ and Sibylle Herzog*
*Institut für Virologie, Giessen, Germany; †Institut für Veterinär-Pathologie Giessen, Germany; and ‡Universität Ulm, Günzburg, Germany Address for correspondence: Jürgen A. Richt, Institut für Virologie, Frankfurterstrasse 107, D-35392 Giessen, Germany; fax: 49-641-99-38359; e-mail: email@example.com.
The geographic distribution and host range of Borna disease (BD), a fatal neurologic disease of horses and sheep, are larger than previously thought. The etiologic agent, Borna disease virus (BDV), has been identified as an enveloped nonsegmented negative-strand RNA virus with unique properties of replication. Data indicate a high degree of genetic stability of BDV in its natural host, the horse. Studies in the Lewis rat have shown that BDV replication does not directly influence vital functions; rather, the disease is caused by a virus-induced T-cell–mediated immune reaction. Because antibodies reactive with BDV have been found in the sera of patients with neuropsychiatric disorders, this review examines the possible link between BDV and such disorders. Seroepidemiologic and cerebrospinal fluid investigations of psychiatric patients suggest a causal role of BDV infection in human psychiatric disorders. In diagnostically unselected psychiatric patients, the distribution of psychiatric disorders was found to be similar in BDV seropositive and seronegative patients. In addition, BDV-seropositive neurologic patients became ill with lymphocytic meningoencephalitis.
In contrast to others, we found no evidence is reported for BDV RNA, BDVantigens, or infectious BDV in peripheral blood cells of psychiatric patients.
Emerging Infectious Diseases 346 Vol. 3, No. 3, July–September 1997 Synopses BDV infections of the CNS with immunopathologic lesions, the same …
Activated Borna disease virus in affective disorders.
- 1Department of Gerontopsychiatry, Free University of Berlin, Germany. firstname.lastname@example.org
Borna disease virus (BDV) is an animal pathogen that causes behavioral changes in animals. Previous studies have found a high prevalence of serum antibodies as well as Borna disease viral antigens (BDVAGs) and RNA in the white blood cells of psychiatric patients, especially those with affective disorders. The present study attempts to offer a better description of the BDVAG cohort using clinical parameters.
The prevalence of BDVAG was examined in the peripheral mononuclear leukocytes of patients with a major depressive episode. A subgroup of patients underwent further clinical analysis.
In this pilot study, at least, there was a significant difference in the prevalence of BDVAG between psychiatric inpatients with a major depressive episode and control individuals. It also appeared that BDVAG is more frequent in patients with recurrent major depression or bipolar disorder than in those with any other psychiatric disorder studied. The number of previous depressive episodes, as well as symptoms involving fatigue and concentration difficulties were positively related to BDVAG.
The high rate of BDVAG, especially in fatigued patients with recurrent major depression or bipolar disorder, may be a nonspecific aspect of immunosuppression. The question remains whether this neurotropic virus may contribute to the pathogenesis of some types of affective disorder.
- [PubMed – indexed for MEDLINE]
Amantadine in depressive patients with Borna disease virus (BDV) infection: an open trial.
- 1Department of Clinical Psychiatry and Psychotherapy, Medical School Hannover, Germany. email@example.com
Originally introduced into pharmacotherapy as an antiviral compound, amantadine was shown to also have multiple pharmacological eftfects on the central nervous system. In addition. only a few studies reported on certain antidepressive properties of amantadine. This effect was highlighted by the discovery of its antiviral effect on Borna disease virus (BDV), which is hypothesized to be an etiopathogenetic factor to subtypes of affective disorders. Therefore, the therapeutical use of amantadine in BDV-infected depressive patients was investigated.
In this open trial, amantadine was added to antidepressive and or mood-stabilizing compounds treating BDV-infected depressed patients (n = 25) with bipolar or major depressive disorders. Amantadine was given twice a day (100-300 mg/day) for a mean of 11 weeks. Antidepressive treatment response was measured on the Hamilton rating scale for depression (HAM-D) and/or with an operationalized diagnostic criteria system (OPCRIT: version 3.31). Virological response was measured by expression of BDV infection parameters in blood samples.
The overall response rate of the amantadine augmentation in the BDV-infected patients with regard to depressive symptoms was 68% after a mean of 2.9 weeks of treatment. Bipolar I patients improved faster and did not show any following hypomania. In addition, the decrease of depression tended to correspond with the decrease in viral activity.
Amantadine appears to show a remarkable antidepressive efficacy in BDV-infected depressive patients. The antidepressive effect in this open trial appeared to be comparable to standard antidepressives, possibly being a result of its antiviral effect against BDV as a potentially relevant etiopathogenetic factor in these disorders.
- [PubMed – indexed for MEDLINE]
And of course a study from Columbia University Mailman School of Public Health that refutes all this. Don’t thow away your medications just yet.
Does Borna Disease Virus Cause Mental Illness?
Over the past 30 years, numerous studies have linked Borna disease virus (BDV) with mental illnesses such as bipolar disorder, schizophrenia, anxiety disorder, and dementia. Genetic fragments and antibodies to this RNA virus, which causes behavior disorders in a range of mammals and birds, have been found to be prevalent in psychiatric patients, but study results have been inconsistent. Now, the first blinded, case-control study to examine this issue finds no association between the virus and psychiatric illness.
The study, conducted by researchers at the Center for Infection and Immunity at Columbia University’s Mailman School of Public Health and collaborators at seven other institutions in the U.S., Germany and Australia, can be found online at Molecular Psychiatry.
The scientists evaluated 198 patients in California with schizophrenia, bipolar disorder, and major depressive disorder, carefully matched each one of them with a healthy control of the same sex, age, region, and socio-economic status, and tested blood of patients and controls for the presence of BDV genetic material and antibodies to BDV.
The investigators hypothesized that if the virus was, in fact, associated with a psychiatric disorder, genetic evidence of infection would be apparent in blood samples taken at the onset and/or at the peak of a psychiatric episode, and antibody evidence would be detectable several weeks afterward. Blood samples were therefore collected within six weeks of the onset of an acute episode or clinically significant worsening of symptoms and six weeks later to allow for changes in viral load or antibody levels. Not only did the researchers find no relationship between mental illness and bornavirus, they found no evidence of active or historical infection with BDV in any of the subjects.
“Our study provides compelling evidence that bornaviruses do not play a role in schizophrenia or mood disorders,” says Mady Hornig, MD, director of translational research at the Center for Infection and Immunity.
In a commentary in the same issue of the journal, Michael B.A. Oldstone, MD, an expert in molecular virology and central nervous system infections at the Scripps Research Institute, observes that the design and experimental procedures carried out in the Hornig study provide a gold standard for investigating links between persistent viral infection and human disease.
CII director, W. Ian Lipkin, MD, senior author of the paper, notes that “it was concern over the potential role of BDV in mental illness and the inability to identify it using classical techniques that led us to develop molecular methods for pathogen discovery. Ultimately these new techniques enabled us to refute a role for BDV in human disease. But the fact remains that we gained strategies for the discovery of hundreds of other pathogens that have important implications for medicine, agriculture, and environmental health.”