Context-dependent role of human immunodeficiency virus type 1 auxiliary genes in the establishment of chronic virus producers. 1993

F Mustafa, and H L Robinson
Department of Molecular Genetics, University of Massachusetts Medical Center, Worcester 01655.

Two molecularly cloned viruses, human immunodeficiency virus type 1 (HIV-1)-NL4-3 (NL4-3) and HIV-1-HXB-2 (HXB-2), have been used to study the role of HIV-1 auxiliary genes in the establishment of chronic virus producers. NL4-3 encodes all known HIV-1 proteins, whereas HXB-2 is defective for three auxiliary genes: vpr, vpu, and nef. Studies were done in H9 cells, a T-cell line unusually permissive for the establishment of chronic virus producers. NL4-3 and HXB-2 undergo lytic phases of infection in H9 cultures with HXB-2, but not NL4-3, supporting the efficient establishment of chronic virus producers. Tests of mutant NL4-3 genomes containing various combinations of defective auxiliary genes revealed that both vpr and nef limited the ability of NL4-3 to establish chronic virus producers. Tests of a series of recombinants between NL4-3 and HXB-2 revealed that 5' internal sequences as well as fragments containing defective auxiliary genes affected the establishment of chronic virus producers. Viral envelope sequences and levels of virus production did not correlate with the ability to establish chronic virus producers. These results suggest that complex interactions of viral auxiliary and nonauxiliary gene functions with the host cell determine the ability to establish chronic virus producers.

UI MeSH Term Description Entries
D003001 Cloning, Molecular The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells. Molecular Cloning
D003588 Cytopathogenic Effect, Viral Visible morphologic changes in cells infected with viruses. It includes shutdown of cellular RNA and protein synthesis, cell fusion, release of lysosomal enzymes, changes in cell membrane permeability, diffuse changes in intracellular structures, presence of viral inclusion bodies, and chromosomal aberrations. It excludes malignant transformation, which is CELL TRANSFORMATION, VIRAL. Viral cytopathogenic effects provide a valuable method for identifying and classifying the infecting viruses. Cytopathic Effect, Viral,Viral Cytopathogenic Effect,Cytopathic Effects, Viral,Cytopathogenic Effects, Viral,Effect, Viral Cytopathic,Effect, Viral Cytopathogenic,Effects, Viral Cytopathic,Effects, Viral Cytopathogenic,Viral Cytopathic Effect,Viral Cytopathic Effects,Viral Cytopathogenic Effects
D004252 DNA Mutational Analysis Biochemical identification of mutational changes in a nucleotide sequence. Mutational Analysis, DNA,Analysis, DNA Mutational,Analyses, DNA Mutational,DNA Mutational Analyses,Mutational Analyses, DNA
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D015752 Genes, env DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein ( HIV rev-Responsive Element,env Genes,rev-Responsive Element,env Gene,Element, HIV rev-Responsive,Element, rev-Responsive,Elements, HIV rev-Responsive,Elements, rev-Responsive,Gene, env,HIV rev Responsive Element,HIV rev-Responsive Elements,rev Responsive Element,rev-Responsive Element, HIV,rev-Responsive Elements,rev-Responsive Elements, HIV
D015754 Genes, nef DNA sequences that form the coding region for a protein that down-regulates the expression of human immunodeficiency virus (HIV). nef is short for negative factor. HIV-3'-orf Genes,nef Genes,Gene, HIV-3'-orf,Gene, nef,Genes, HIV-3'-orf,HIV 3' orf Genes,HIV-3'-orf Gene,nef Gene
D016334 Genes, vpr DNA sequences that form the coding region for a trans-activator protein that specifies rapid growth in human immunodeficiency virus (HIV). vpr is short for viral protein R, where R is undefined. Genes, R,Genes, rap,vpr Genes,vpr Gene,Gene, R,Gene, rap,Gene, vpr,R Gene,R Genes,rap Gene,rap Genes
D016338 Genes, vpu DNA sequences that form the coding region for the HIV-1 regulatory protein vpu (viral protein U) that greatly increases the export of virus particles from infected cells. The vpu genes are not present in HIV-2 or SIMIAN IMMUNODEFICIENCY VIRUS. vpu Genes,Gene, vpu,vpu Gene

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