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Biomedical subjects

A T Haase

Publications and source records attributed to A T Haase.

At least 91 records · Page 5Linked to original sources
PubMed1981

Gene expression in visna virus infection in sheep.

Visna is a slow degenerative disease of the central nervous system (CNS) of sheep caused by a nontumorigenic retrovirus. During the course of this disease, visna virus establishes a persistent infection of the CNS, lung and haematopoietic system, despite a specific humoral and cellular immune response. We have studied visna virus life cycle at the single-cell level in choroid plexus of experimentally infected animals, using a very sensitive and quantitative in situ hybridization assay. We report here that although proviral DNA is synthesized in significant amounts, its expression is blocked at the transcriptional level. This restriction of proviral DNA transcription offers an explanation for the slowness of the disease and the persistence of the infection.

Animals↗
PubMed1981

Measles virus nucleotide sequences: detection by hybridization in situ.

A tritium-labeled probe that detects measles virus nucleotide sequences was hybridized in situ to cells infected with measles virus and to sections of brain tissue from patients with subacute sclerosing panencephalitis and from patients with multiple sclerosis. The measles virus genome was detected in many cells in subacute sclerosing panencephalitis where this virus would have been missed by methods such as immunofluorescence. Measles virus sequences were also found in two foci in one of four cases of multiple sclerosis. This refined method of hybridization in situ, which can be useful in the search for covert virus infections of man, provides evidence that viruses may be involved in multiple sclerosis.

Adolescent↗
PubMed1981

Measles virus genome in infections of the central nervous system.

The measles virus genome was traced in acute and chronic infections of the central nervous system in hamsters and humans. The extent of viral replication and gene expression was assessed by the techniques of in situ hybridization and immunofluorescence. Both replication and gene expression were restricted in chronically infected hamsters and in humans with subacute sclerosing panencephalitis. It is proposed that restriction plays an important role in persistence of measles virus and the slow evolution of disease in these and other slow infections.

Acute Disease↗
PubMed1979

Antigenic variation in visna virus.

Two antigenic variants of visna virus were isolated sequentially from a single sheep inoculated with a plaque-purified strain of virus designated 1514. The genetically stable variants, LV1-1 and LV1-4, are of two classes: LV1-1 is partially neutralized by antibody to the inoculum strain 1514, while LV1-4 is not neutralized by antibody to 1514. The genetic mechanism responsible for generating the antigenic variants was investigated by comparing the chymotryptic and tryptic maps of the envelope glycoprotein gp135 and core polypeptides (p30, p16, p14), and by comparing the pattern of large oligonucleotides produced by digestion of the RNAs by T1 ribonuclease. We show that only the peptide maps of gp135 differ among strains, that the number of peptide fragments altered is small and that gp135 is the polypeptide that elicits neutralizing antibody. The maps of the RNAs are identical. We conclude that mutation in the glycoprotein gene rather than recombination is more probably responsible for antigenic variation, and speculate on the special aspects of visna virus replication relevant to this phenomenon.

Amino Acid Sequence↗
PubMed1979

Serological definition of the lentivirus group of retroviruses.

The major polypeptides of visna viruses and other lentiviruses have been isolated and shown to be closely related if not identical in radioimmunoassays. By this criterion the lentiviruses form a distinct group of retroviruses unrelated to spuma viruses, mammalian and avian retroviruses that cause tumors, and unclassified retroviruses of cattle and horses. Two sera obtained from goats immunized with Mason-Pfizer monkey virus or squirrel monkey virus reacted with visna p30. Additional data suggest that this reaction represents infection of goats with a lentivirus or a new retrovirus closely related to the lentiviruses.

Animals↗
PubMed1978

Detection of viral sequences of low reiteration frequency by in situ hybridization.

The sensitivity of in situ hybridization has been increased at least 10-fold by hybridizing in cDNA excess, by increasing the diffusion of the cDNA through the cells, by hybridizing at optimum temperature, and by stabilizing hybrids during autoradiography. Saturation of intracellular RNA with [3H]cDNA has been achieved. The assay is quantitative. In situ hybridization has been used to detect and quantitate visna virus RNA in infected cells. By using [3H]cDNA with specific activity of 2 X 10(8) dpm/micrograms and conditions that reduce background to negligible levels, 10--20 copies of viral RNA per cell can be detected and quantitated after 2 days of autoradiographic exposure.

Animals↗
PubMed1978

Polyoma virus-human cell interactions: persistence of T-antigen in two cell lines with and without transformation.

The interaction of polyoma virus and human cells was investigated. Abortive infection as evidenced by the synthesis of T-antigen was observed in normal fibroblast and abnormal (transformed) cells but not in normal epithelial cells. A high percentage of simian virus 40-transformed WI-18 Va2 and spontaneously transformed BE skin cells produced T-antigen after high-multiplicity infection, but most of the cells rapidly lost antigen-producing capacity upon cell passage, and the cultures became negative by passage 3. All fibroblast cells displayed varying degrees of susceptibility to infection, but most of the cell lines became negative for T-antigen except for two. In one, T-antigen persisted in a small percentage of the cells throughout the lifetime of the culture, without cellular transformation occurring. In the other, the entire culture became morphologically transformed and eventually consisted of 100% T-antigen-positive cells. This is the first time that normal diploid human fibroblast cells have been transformed by polyoma virus.

Animals↗
PubMed1977

Slow persistent infection caused by visna virus: role of host restriction.

Proviral DNA has been demonstrated by in situ hybridization in foci of cells of a lamb infected with the RNA slow virus visna. A few of these cells also contain the major virion structural antigen p30. This restriction in virus gene expression in the infected animal provides a mechanism for persistence of virus in this chronic infection.

Animals↗
PubMed1977

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↗