AIDS Research at the NIH: A Critical Review

regulatory element within the promoter regions of the IL-1 R-alpha gene and the homologous element in
the HIV-1 LTR has been purified and found to be under the control of a cytoplasmic inhibitor. The activation
of this protein is inhibited by cyclosporin A. Laboratory of Molecular Pharmacology: Effects of UV light
and other stressors on HIV replication. Laboratory of BIochemical Physiology: Hsiang-fu Kung, PhD:
Cytokines and HIV+ macrophages. Laboratory of Experimental Immunology: NK cells, CTL and
cytokines. Surgery Branch: Steven Rosenberg, MD, PhD: Adoptive immunotherapy for AIDS. Laboratory
of Medicinal Chemistry: Fluoro-ddNs. Laboratory of Biochemical Pharmacology: Chain terminators
III. Developmental Therapeutics Program: Antiretroviral compounds from the Euphorbiaceae; a marine
sponge and a tunicate, Buchenavia capitata; a xanthophyll with anti-HIV activity; anti-HIV dimeric alkaloids
from Ancistrocladus spp.; antiviral plant diterpenes.
DIVISION OF CANCER ETIOLOGY (DCE). Environmental Epidemiology Branch (EEB). William
Blattner, MD: Epidemiology of human lymphotropic viruses - Adult T-Cell Leukemia, AIDS and cancer.
Laboratory of Comparative Carcinogenesis: Jerrold Ward, DVM, PhD: Biology of natural and
experimentally-induced tumors. Laboratory of Experimental Carcinogenesis: Aminoacyl-tRNAs in HIV+
cells. Blostatistics Branch: Mitchell Gail, MD, PhD: Projecting incidence of AIDS-related NHL through
1992; assisting members of the Viral Epidemiology Section on the design, conduct, and analysis of the
studies of the natural history of HIV and of biological markers. Laboratory of Molecular Oncology: DNA
topoisomerase I activity in retroviruses. See if topoisomerases play a role in retroviral life cycles and if
these enzymes might be a target for therapy. In vitro, a specific topoisomerase I inhibitor, camptothecin,
blocked HIV infection of uninfected cells and inhibited EIAV production in chronically infected cells.
Laboratory of Cellular and Molecular Biology: Dharam Ablashi, DVM: HHV-6, EBV and HIV. Activation
of latent HHV-6 infection in PWAs, people with CFS, SLE and BMT. HHV-6 induction of IL-1-beta and TNFalpha in human PBMC. HHV-6 antigen also present in Hodgkin's disease and Sjogren's syndrome, African
and American Burkitt's lymphomas. Steven Tronick, PhD: Studies in the gene expression of EIAV and
CAEV. Laboratory of Molecular Virology: Jeffrey Green, MD: Gene therapy for HIV and HTLV-I using
HIV LTR-HSV thymidine kinase construct in defective retroviral vector. Stem cells transformed with the
construct and subsequently infected with HIV should be able to be selectively killed with acyclovir, while
allowing uninfected cells to replenish the T-cell population. Laboratory of Viral Carcinogenesis: Human
genetic loci which influence susceptibility to HIV. Vaccines, epitopes, pig-tailed macaques, genetic drift in
SIV+ monkeys. Challenge stocks. Dean Mann, MD: association of HLA antigens with disease progression
and outcome in individuals with HIV infection. Biological Carcinogenesis Program: Edward Tabor, MD:
Inhibition by desferrioxamine of in vitro replication of HIV-1: Desferrioxamine, an iron-chelating agent used
as an antidote in iron poisoning, was shown to inhibit HIV-1 replication in vitro, possibly by interfering with
RNA-dependent DNA synthesis.
Laboratory of Tumor Cell Biology: Robert Gallo, MD: Studies on T cell malignancies, lymphomas and
AIDS. KS studies showed growth of KS cells is enhanced by corticosteroids; AIDS-KS cells secrete factors,
which induce angiogenesis, increase vascular permeability; AIDS-KS cells produce IL-6, and IL-8; AIDS-KS
cells have high affinity receptors for IL-1, IL-2, 11-6, PDGF, BFGF, TNF, hydrocortisone, the HIV-1 Tat
protein and Oncostatin M; ability of SPPG to inhibit KS growth and development in vitro and in a mouse
model. Mechanisms of HIV-1 pathogenesis: Studies of the role of cytokine production by
monocyte/macrophages in disease pathogenesis which have discovered: macrophages infected with HIV
produce factors which accelerate the proliferation of cells derived from the synovial lining of uninfected
individuals. Quantitation of cytokines from supematants from infected macrophages showed that although
several cytokines were expressed, none were present in amounts adequate to explain the proliferation of
test cells and therefore, monocytes/macrophages may produce substimulatory concentrations of cytokines
which may act additively or synergistically; the interaction between HHV-6 and HTLV-1 and HIV-1 results
in an expanded host cell range due to phenotypic mixing of the viruses as well as the modulation of CD
antigens on infected cells. HHV-6 infection increases the surface density of the CD4 antigen as well as
de novo expression on otherwise CD4- cells.
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