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O Narayan

Publications and source records attributed to O Narayan.

At least 109 records · Page 6Linked to original sources
PubMed1993

Genomic organization of the structural proteins of borna disease virus revealed by a cDNA clone encoding the 38-kDa protein.

Borna disease is a rare neurological disease of sheep and horses. The etiological agent, borna disease virus (BDV), has been shown to be an RNA virus but has not been characterized sufficiently to assign it to a virus family. Previous studies have shown that three BDV-specific proteins of 14, 24 and 38 to 39 kDa are found in infected animals and cell culture (Ludwig et al., 1988, Prog. Med. Virol. 35, 107-151). cDNA clones have been isolated that encode the 14- and 24-kDa proteins; using the nucleotide sequences from these clones additional cDNAs were isolated that contained a large open reading frame (ORF) corresponding to the 38-kDa protein. Monoclonal antibodies against the BDV 38- to 39-kDa protein recognized the protein product of the large ORF. The relative gene order of the three BDV proteins (5' 38, 14, and 24 kDa 3') can be deduced from cDNAs which include portions of both the 24- and 38-kDa ORFs. The abundance of these proteins in BDV-infected animals and cultured cells suggests that these proteins are structural components of the virus. Previously all BDV-specific mRNAs (10.5, 3.6, 2.1, and 0.85 kb) were thought to be organized as overlapping 3' coterminal RNAs. Oligonucleotide probes made to the nucleotide sequence of the cDNA that encodes the 38-kDa protein identified an additional BDV-specific mRNA of 1.4 kb. This 1.4-kb mRNA species partially overlaps with the 2.1-kb RNA but is not 3' coterminal.

Amino Acid Sequence↗
PubMed1993

Antigenic variation of molecularly cloned SIVmac239 during persistent infection in a rhesus macaque.

Eight rhesus macaques inoculated with molecularly cloned SIVmac239 developed viremia and virus-binding antibodies, but only one (macaque 2D) developed neutralizing antibodies to the virus. Viremia persisted in macaque 2D even in the presence of neutralizing antibodies. Neutralizing antibodies in the plasma collected from macaque 2D late in infection neutralized virus isolated early in infection. In contrast, these antibodies failed to neutralize the plasma viruses isolated after the appearance of neutralizing antibodies. Only antigenic variants were isolated from blood, spleen, and lymph nodes. Viruses isolated from other macaques that did not develop neutralizing antibodies were neutralized by 2D serum and were of the parental (SIVmac239) phenotype. The variant viruses maintained their strict tropism for lymphocytes, similar to the parental virus.

Animals↗
PubMed1993

Analysis of envelope changes acquired by SIVmac239 during neuroadaption in rhesus macaques.

Nucleotide sequence analyses of the env genes of two neurotropic variants of SIVmac239 were performed to determine whether molecular changes in these genes could be correlated with neurotropism. Biological characterization of virus from the infectious molecular clone of SIVmac239 had shown that it is highly lymphocyte-tropic and poorly macrophage-tropic. This virus failed to replicate in the brain after intracerebral inoculation, but passage of this virus in macaques resulted in development of viral variants that had acquired cell tropism for macrophages and were neurovirulent (D. P. Sharma, M. C. Zink, H. Anderson, R. J. Adams, J. E. Clements, S. V. Joag, and O. Narayan, J. Virol., 66, 3550-3556, 1992). The neurotropic virus SIVmac239/R71 was obtained from the brain of a monkey after the third in vivo passage of SIVmac239. Inoculation of this virus into another macaque leads to CNS disease and the isolation of another neurotropic virus SIVmac239/17E. The viral env sequences obtained by polymerase chain reaction amplification directly from DNA obtained from the brain of R71 and 17E macaques had a limited number of changes dispersed throughout the env gene when compared to the parental virus, SIVmac239. The most important finding was that there was a common set of nucleotide changes in the env gene of both R71 and 17E. This suggested that viruses containing these changes had a selective growth advantage in the brain and were the predominant species present in the central nervous system of macaques R71 and 17E. Analysis of individual clones containing the R71 env gene revealed that different env genes were present, but all had the changes that were conserved in both R71 and 17E but not present in the original lymphocyte-tropic parental virus, SIVmac239. Construction of an infectious recombinant virus containing the tat, rev, and env genes from 17E and the remainder of the genome from the parental virus SIVmac239 resulted in a virus that had the macrophage-tropism of 17E virus isolated from brain. This demonstrates that the env gene of 17E confers the cellular tropism of the virus on the parental virus, SIVmac239.

Amino Acid Sequence↗
PubMed1993

Borna disease virus: nature of the etiologic agent and significance of infection in man.

This review presents data on the characterization of Borna disease virus (BDV) and its potential as a possible causative agent in humans. The isolation of: (i) BDV-specific cDNA clones that encode various BDV-specific proteins and (ii) partially purified virus particles led to the conclusion that the viral genome consists of negative-sense, single-stranded RNA. The organization of the BDV-specific RNA species appears to be a nested set of overlapping subgenomic RNA transcripts. Furthermore, evidence is presented that BDV can infect humans and may cause certain psychiatric and neurological disorders. This concept is supported by: (i) the finding of virus-specific antibodies in sera of patients with neuropsychiatric diseases and (ii) results obtained during attempts to isolate BDV or a BDV-related agent from the cerebrospinal fluid of seropositive patients.

Animals↗
PubMed1993

Immunodeficiency-inducing retroviruses.

The plethora of disease syndromes (dystrophy of various organ systems, malignancies and opportunistic infections) caused by HIV are all potentiated by the profound virus-induced immunosuppression that accompanies this infection. The mechanism of this severe immunosuppression is poorly understood and the subject is currently being pursued in studies of HIV-infected patients and in animals infected with other immunodeficiency-inducing retroviruses.

Animals↗
PubMed1993

Comparison of the effects of 3'-azidothymidine with those of neutralizing antibodies on simian immunodeficiency virus infection in macrophages.

We previously showed that simian immunodeficiency virus-infected macaque macrophages contacting uninfected CD4+ lymphocytes caused extensive cell fusion and synthesis of phlogistic cytokines. In this study, macaque macrophage cultures inoculated with SIVmac251 and treated simultaneously with 10 microM 3'-azidothymidine (AZT) became infected and produced small amounts of viral antigen (p27) but failed to fuse with CD4+ CEM174 cells. When AZT was added 1 to 3 days after virus inoculation, the infected cells caused fusion and the release of tumor necrosis factor and produced increasing amounts of p27. In contrast, neutralizing antibodies prevented infection when added at the time of virus inoculation, and they were much more effective than AZT in limiting virus replication, fusion cytopathic effect, and cytokine production when added up to 3 days postinoculation. Neutralizing antibodies may be more effective than AZT in reducing the virus load in the macrophage population and in preventing both cell fusion and the production of potentially pathogenic cytokines.

Animals↗
PubMed1992

Human immunodeficiency virus infection in microglia: correlation between cells infected in the brain and cells cultured from infectious brain tissue.

In acquired immunodeficiency syndrome, the lesions of the central nervous system in association with the human immunodeficiency virus are thought to be related to an infection of microglia, although no studies are available in which cultured and physiological characteristics of microglia cells infected in vivo have been examined. In this report, we used brain tissue from a child dying of human immunodeficiency virus infection and show that microglia cells were the main cell population being infected. Moreover, isolated macrophage-like cells from fresh brain material revealed a close resemblance to peripheral blood macrophages in their content of surface and intracellular antigens. No virus particles or viral antigens were produced by these cells during the first week of cultivation. Productive infection was readily apparent, however, by day 30. This finding illustrates the slow nature of the virus life cycle in these cells and the minimal cytopathology that accompanied the infection.

Brain↗
PubMed1992

Differences in neutralization of simian lentivirus (SIVMAC) in lymphocyte and macrophage cultures.

Comparison of neutralization of SIVmac251 in primary macrophage cultures with neutralization in lymphocytes (CEM174 cells) showed that neutralizing antibodies induced by SIV251 in infected rhesus macaques protected both macrophages and T lymphocytes against infection when the virus was preincubated with the antibodies. In macrophages, the neutralizing antibodies also protected against infection when added 1 hour after the virus. Addition of antisera to macrophages between 24 and 48 hours after virus inoculation resulted in infection with continuous release of small amounts of p24 into the supernatant fluids but these antibody-treated cultures failed to exhibit cytopathic virus replication. In contrast, the same neutralizing antisera did not protect lymphocytes against infection and subsequent cytopathic replication of the virus when added only 1 hour after virus inoculation. This distinction in the effect that neutralizing antibodies had on the development of cytopathic infection in lymphocytes and macrophages when added after virus inoculation, suggests that they could alter the dynamics of virus replication and therefore the pathogenesis of disease.

Animals↗
PubMed1992

Infection with Borna disease virus: molecular and immunobiological characterization of the agent.

Borna disease virus (BDV), which seems to be distinct from all other known viruses, exhibits a unique mechanism of pathogenesis. This review highlights several aspects of the biology of infection with this virus and summarizes the preliminary characterization of the agent. Studies on BDV may help to illuminate several important areas of neurobiology, including the mechanisms regulating the replication of a new type of RNA virus in the nuclei of neural cells, the neuroinvasiveness and neurotropism of such viruses, their T cell-mediated immunopathology, tolerance in newborn animals to persistent viral infection of the central nervous system, and behavioral diseases and eating disorders induced by such agents.

Animals↗
PubMed1992

Pathogenesis of acute infection in rhesus macaques with a lymphocyte-tropic strain of simian immunodeficiency virus.

The simian immunodeficiency virus, SIVmac, causes disease affecting multiple organ systems in macaques similar to human immunodeficiency virus infection in humans. Molecularly cloned SIVmac with a strong lymphocyte tropism was used in pathogenesis experiments to correlate viral cell tropism with disease. In 5 animals, exhaustive analyses on viruses from tissues and identification of infected precursor cells were done at multiple times during infection to ensure the virus had not mutated into a macrophage-tropic variant. Viral replication was measured by infectivity, infectious center assays, and in situ hybridization. Lymphocytes produced most virus in tissues, indicating the virus maintained its cell tropism in vivo. Lymphocytes in bone marrow were latently infected and those in the spleen and lymph nodes were productively infected. The virus failed to replicate in the brain after intracerebral inoculation. SIVmac that maintained a strong tropism for lymphocytes and a corresponding poor tropism for macrophages can cause persistent infection and AIDS but not other diseases such as primary pneumonia and encephalitis in rhesus macaques.

Acute Disease↗
PubMed1992

Tumour necrosis factor and interleukin 6 production during interaction between activated CD4+ lymphocytes and simian immunodeficiency virus-infected macrophages.

The mechanism for the gradual loss of CD4+ T lymphocytes and the development of the slowly progressive inflammatory/degenerative lesions that accompany human immunodeficiency virus infection are poorly understood. Using the Simian immunodeficiency virus (SIVmac) macaque model of AIDS, we found that persistently infected primary macrophages fuse with primary activated CD4+ lymphocytes and that this interaction results in production of tumour necrosis factor-alpha (TNF alpha) and interleukin 6 (IL-6). An earlier report had shown that SIV-infected macaque macrophages fuse with CEM174 cells (a human CD4+ cell line) and cause their lysis. In the present report, we have shown that TNF-alpha and IL-6 are also produced during the early stages of this interaction. Data from cocultivation of infected macrophages with several CD4+ T cell lines, including CEM174, suggested that the cytokines are produced by the T cells, and that cytokine production is restricted to those cells which not only express CD4, but are also capable of fusing with the infected macrophages. These data suggest that infected macrophages in vivo could fuse with and eliminate activated CD4+ lymphocytes and, during this interaction, release cytokines, which would contribute to the degenerative and inflammatory lesions characteristic of this disease.

Animals↗