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Biomedical subjects

M Brahic

Publications and source records attributed to M Brahic.

105 records · Page 6Linked to original sources

Visna virus RNA synthesis.

Visna is a classical slow infection in which virus characteristically persists in the face of the host immune response. The agent of this disease belongs to the retravirus group. The persistence of infection and the slow spread of virus are at least in part a consequence of restriction of the expression of virus genetic information in tissues of an infected animal (A. T. Haase et al., Science 195:175-177, 1977), but the point at which the virus life cycle is interrupted in vivo and the mechanism of restriction are unknown. We have embarked on a molecular analysis of restriction, focusing first on transcription. In this paper we have established the levels of viral RNA synthesis under permissive conditions, as a base line for subsequent studies in vivo. We show that (i) uninfected cells do not contain RNA sequences related to the visna virus genome, (ii) parental RNA is rapidly transported to the nucleus of the infected cell, (iii) virus RNA is synthesized in the nucleus and then transported to the cytoplasm (iv) synthesis of RNA proceeds mostly exponentially to reach levels of about 4,000 copies per cell at the end of the growth cycle, (v) nuclear and cytoplasmic RNA sediment in two size classes, 35S and 10-20S, (vi) viral mRNA has the same polarity as genome RNA and also sediments in two size classes of 35S and 10-20S.

Animals↗

Isolation and characterization of a basic encephalitogenic protein from the central nervous system of sheep.

A basic protein has been purified from sheep brain. The purified protein sedimented in the analytical centrifuge at 56,000 r.p.m. as an homogenous product. This protein induced an allergic encephalitis when injected into guinea pigs. Some physiochemical properties of the protein were studied: the sedimentation coefficient was 1.52 and the molecular weight was 20,000 +/- 2,000, as estimated by electrophoresis in acrylamide gels containing SDS and urea; the specific extinction coefficient (see article) was 6.01 +/- 0.20. The aminoacid composition of the molecule was determined and its most prominent aspects are a high content of arginine and lysine, the presence of a single tryptophan, the total absence of cysteine and cystine and a blocked N-terminal residue. All these properties are very close to those of human and bovine encephalitogenic proteins.

Amino Acids↗

Properties of visna virus particles harvested at short time intervals: RNA content, infectivity, and ultrastructure.

The major RNA component of Visna virus harvested at short intervals of time (5 min) is not the 60 to 70S RNA but a molecule of higher electrophoretic mobility. This RNA has been isolated and characterized. Its sedimentation coefficient is identical to that of 30 to 40S RNA subunits obtained by heat denaturation of the 60 to 70S RNA. In 1.8% acrylamide gels without agarose the electrophoretic mobility of 30 to 40S RNA subunits present in rapidly harvested virus is slightly lower than that of the subunits obtained by denaturation of the 60 to 70S RNA; after heat denaturation the mobilities are identical. These free RNA subunits present in early virus particles assemble into a 60 to 70S RNA complex as shown by following the RNA content of early virus incubated at 37 C for various lengths of time. The rate of this maturation process is slow. There is no difference between the infectivity of immature and mature virus particles. Both particles have a dense core when examined in sections of virus pellets.

Journal Article↗

Analysis of human T-lymphotrophic virus sequences in multiple sclerosis tissue.

Several observations suggest that retroviral infection is involved in the pathogenesis of the human demyelinating disease multiple sclerosis (MS). First, lymphadenopathy-associated virus/human T-lymphotropic virus type III (LAV/HTLV-III), the agent of acquired immune deficiency syndrome (AIDS), has been shown to be neurotropic in man. Second, the genetic organization of the lentivirus visna, which causes a chronic demyelinating disease of sheep, closely resembles that of LAV/HTLV-III. Recently, Koprowski and colleagues reported that MS is associated both with raised levels of circulating antibodies to HTLV-I and with the presence of HTLV-I-specific RNA within cell lines derived from the cerebrospinal fluid (CSF). Here we report that no HTLV-I-like or LAV/HTLV-III-like sequences can be detected, by in situ hybridization, in central nervous system (CNS) tissues from MS patients, and that nonspecific HTLV-I-like signal in peripheral blood mononuclear cells or in CSF cell lines is characteristic of MS. Furthermore, enzyme-linked immunosorbent assay (ELISA) analysis of circulating and CSF antibodies for HTLV-I reactivity fails to distinguish between MS and control groups.

Antibodies, Viral↗