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M D Hoggan

Publications and source records attributed to M D Hoggan.

8 recordsLinked to original sources

Replication of HIV-1 and HIV-2 in human bone marrow cultures.

The bone marrow is a target organ for the human immunodeficiency virus (HIV), but the mechanisms by which suppression of hematopoiesis occurs during the course of HIV infection are not well understood. To study this issue, the effect of several different HIV-1 isolates (monotrophic and lymphotrophic) and one HIV-2 isolate on in vitro colony formation by BFU-E and CFU-GM from normal human marrow were examined. The monotrophic strain AD-87 (M) failed to replicate in marrow cultures as documented by RT, and colony formation by BFU-E and CFU-GM was unaffected by this virus. A derivative of this isolate AD-87 (M-P), which was replicated in peripheral blood lymphocytes (PBL), however, replicated well and markedly inhibited colony formation by BFU-E and CFU-GM. Two additional PBL isolates replicated less efficiently; neither inhibited CFU-GM but one consistently inhibited BFU-E colony formation. Inhibition of colony formation by the HIV-1 isolates was a late event, presumably a secondary lysis of cells, since up to 7 days after inoculation colony numbers were normal but diminished markedly by 10 days, and since only up to 10% of the cells of the monocyte lineage contained detectable virus by in situ, EM, and IFA studies. In contrast, the HIV-2 isolate was so lytic that by 4 days after inoculation the majority of the marrow cells were destroyed.

Bone Marrow

A novel HIV-1 isolate containing alterations affecting the NF-kappa B element.

Three molecular clones of HIV-1, derived from a single isolate (AL1), exhibited distinct replicative and cytopathic properties during propagation in a human T cell line. The phenotypic differences observed were attributable, in large part, to changes affecting the viral LTR. Nucleotide sequence and PCR analyses demonstrated the presence of novel duplications or deletions involving the NF-kappa B motif. These changes in the enhancer element were identified in the original AL1 virus stock. Subcloning of the variant NF-kappa B segments into LTR-driven CAT expression vectors confirmed a correlation between promoter activity and replicative/cytopathic capacity.

Base Sequence

The human immunodeficiency virus type 1-specific protein vpu is required for efficient virus maturation and release.

A deletion mutation affecting vpu was introduced into an infectious molecular clone of human immunodeficiency virus type 1, and the resultant phenotype was examined after infection of human T lymphocytes. The absence of vpu resulted in an accumulation of cell-associated viral proteins and impaired the release of progeny virions. Both electron microscopic and biochemical analyses indicated that a large proportion of the mutant particles was attached to the surface of infected cells. Significant variation in the size and shape of these progeny virions was observed. In addition, intracytoplasmic particles, some of which formed aberrant budding structures, were visualized in T cells infected with the vpu mutant. Indirect immunofluorescence analyses of cultures inoculated with wild-type virus with use of a vpu-specific antiserum demonstrated that vpu is mainly localized to a perinuclear region in the cytoplasm of virus-producing cells.

Amino Acid Sequence

Adenovirus-associated virus structural protein sequence homology.

Adenovirus-associated virus (AAV) structural proteins (VP1, VP2, and VP3) have been examined to determine if areas of sequence homology exist between these three virion proteins. Tryptic and chymotryptic maps have been produced which demonstrate extensive areas of sequence homology common to all three proteins. The amino acid compositions of the proteins were also determined and were found to be very similar. These data are consistent with the hypothesis that all three virion proteins arise either from a common precursor of similar transcripts.

Amino Acid Sequence

Parvoviridae.

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Parvoviridae