Long-term inhibition of human T-lymphotropic virus type III/lymphadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T cells protected by 2',3'-dideoxynucleosides in vitro

Journal Article · Wed Apr 01 04:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.7.2033· OSTI ID:6027544

Mitsuya, H; Jarrett, R F; Matsukura, M; Veronese, F D.M.; DeVico, A L; Sarngadharan, M G; Johns, D G; Reitz, M S; Broder, S

The authors report that 2',3'-dideoxyadenosine and 2',3'-dideoxycytidine inhibit retroviral DNA synthesis and mRNA expression in T cells exposed to the virus that causes acquired immunodeficiency syndrome, and afford such cells long-term protection in vitro under conditions of substantial viral excess. Both 2',3'-dideoxyadenosine and 2'3'-dideoxycytidine appear to completely block reverse transcription from viral RNA to viral DNA. Viral mRNA expression is also not detected in cells protected by the drugs throughout 30 days of culture following exposure to the virus. Purine and pyrimidine analogues as 2',3'-dideoxynucleoside-5'-triphosphate serve as substrates for the human T-lymphotropic virus type III/lymphadenopathy-associated virus reverse transcriptase to elongate a DNA chain by one residue, after which the chain is terminated. Cloned normal helper/inducer T cells exposed to a cytopathic dose of the virus, but protected by the drugs, respond normally to specific antigen in vitro. These results suggest that the drugs could be promising agents for further studies in the experimental treatment of patients infected with retroviruses.

• Research Organization: National Institutes of Health, Bethesda, MD
• OSTI ID: 6027544
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:7; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
ANTIBODIES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHEMISTRY
CHEMOTHERAPY
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DISEASES
DNA REPLICATION
DNA SEQUENCING
IN VITRO
INFECTIOUS DISEASES
INHIBITION
ISOTOPES
LEUKOCYTES
LIGHT NUCLEI
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MESSENGER-RNA
MICROORGANISMS
MONOCLONAL ANTIBODIES
NUCLEI
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PARASITES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
RIBOSIDES
RNA
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
THERAPY
TRANSCRIPTION
VERTEBRATES
VIRAL DISEASES
VIRUSES