Infectious Mutants of HTLV-III with Changes in the 3′ Region and Markedly Reduced Cytopathic Effects

Fisher, Amanda G.; Ratner, Lee; Mitsuya, Hiroaki; Marselle, Lisa M.; Harper, Mary‐Ellen; Broder, Samuel; Gallo, Robert C.; Wong‐Staal, Flossie

doi:10.1126/science.3014663

Cited by 225 publications

(112 citation statements)

References 27 publications

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“…The most obvious product of the PCR analysis represented nefmRNA. This was surprising in view of the putative role of nef as a factor that negatively regulates viral transcription in some (Fisher et al, 1986;Luciw et al, 1987;Ahmad & Venkatesan, 1988;Cheng-Mayer et al, 1989;Niederman et al, 1989) but not all studies (Kim, 1989b). Using a similar PCR system for detecting spliced HIV-1BaL mRNAs in macrophages (but without conducting a time-course analysis), Robert-Guroff et al (1990) also found a strong nefmRNA signal in macrophages that had been infected with HIV-IBaL for 12 to 14 days.…”

Section: Discussionmentioning

confidence: 99%

Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages

Munis

Kornbluth

Richman

1992

Journal of General Virology

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The order of appearance of human immunodeficiency virus type 1 (HIV-1) nucleic acids was examined in monocyte-derived macrophages following a high multiplicity infection with macrophage-tropic virus. Using the polymerase chain reaction, viral DNA was first detected 2 h after infection and continued to accumulate over the next 24 h. Transcripts representing tat, rev and nefsplicing were detected by 24 h, and transcripts representing env splicing were detected by 48 h after infection. Coincident with the appearance of env transcripts, new synthesis of cellular and extracellular p24 antigen began, multinucleated giant cells formed and progeny infectious virus emerged. This analytical system provides a foundation for further studies on the effects of antiviral agents and cellular factors on the replication cycle of HIV-1 in non-transformed, primary monocyte-derived macrophages.

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Section: Discussionmentioning

confidence: 99%

Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages

Munis

Kornbluth

Richman

1992

Journal of General Virology

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“…pGG1 contains a functional clone of HIV-1 (HXB2gpt2 in ref. 9). pGA1 was produced by mutagenesis of the codon encoding Gly-2 in the gag gene of pGG1 to a codon-encoding alanine (4).…”

Section: Methodsmentioning

confidence: 99%

Incorporation of 12-methoxydodecanoate into the human immunodeficiency virus 1 gag polyprotein precursor inhibits its proteolytic processing and virus production in a chronically infected human lymphoid cell line.

Bryant

Ratner

Duronio

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Covalent linkage of myristate (tetradecanoate; 14:0) to the NH2-terminal glycine residue of the human immunodeficiency virus 1 (HIV-1) 55-kDa gag polyprotein precursor (Pr555 ¶9) is necessary for its proteolytic processing and viral assembly. We have shown recently that sever al analogs of myristate in which a methylene group is replaced by a single oxygen or sulfur atom are substrates for Saccharomyces cerevisiae and mammalian myristoyl-CoA:protein N-myristoyltransferase (EC 2.3.1.97; NMT) despite their reduced hydrophobicity. Some inhibit HIV-1 replication in acutely infected CD4' H9 cells without accompanying cellular toxicity.To examine the mechanism of their antiviral effects, we performed labeling studies with two analogs, 12-methoxydodecanoate (13-oxamyristate; 13-OxaMyr) and 5-octyloxypentanoate (6-oxamyristate; 6-OxaMyr), the former being much more effective than the latter in blocking virus production.

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“…The cytoplasmic domain of HIV-1 gp41, spanning residues 706 -856, plays various roles in virus replication, infectivity, transmissibility, and cytopathogenicity (5,(12)(13)(14)(15)(16)(17). The C terminus of the cytoplasmic tail may play a role in viral uncoating or penetration of the viral core into host cells (18).…”

mentioning

confidence: 99%

Multimerization Potential of the Cytoplasmic Domain of the Human Immunodeficiency Virus Type 1 Transmembrane Glycoprotein gp41

Lee¹,

Wang²,

Liang³

et al. 2000

Journal of Biological Chemistry

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We previously demonstrated that an envelope mutant of human immunodeficiency virus type 1 lacking the entire cytoplasmic domain interferes in trans with the production of infectious virus by inclusion of the mutant envelope into the wild-type envelope complex. We also showed that the envelope incorporation into virions is not affected when the wild-type envelope is coexpressed with the mutant envelope. These results suggest that an oligomeric structure of the cytoplasmic domain is functionally required for viral infectivity. To understand whether the cytoplasmic domain of human immunodeficiency virus type 1 transmembrane protein gp41 has the potential to self-assemble as an oligomer, in the present study we fused the coding sequence of the entire cytoplasmic domain at 3 to the Escherichia coli malE gene, which encodes a monomeric maltose-binding protein. The expressed fusion protein was examined by chemical cross-linking, sucrose gradient centrifugation, and gel filtration. The results showed that the cytoplasmic domain of gp41 assembles into a high-ordered structural complex. The intersubunit interaction of the cytoplasmic domain was also confirmed by a mammalian two-hybrid system that detects protein-protein interactions in eucaryotic cells. A cytoplasmic domain fragment expressed in eucaryotic cells was pulled down by glutathione-Sepharose 4B beads via its association with another cytoplasmic domain fragment fused to the C terminus of the glutathione S-transferase moiety. We also found that sequences encompassing the lentiviral lytic peptide-1 and lentiviral lytic peptide-2, which are located within residues 828 -856 and 770 -795, respectively, play a critical role in cytoplasmic domain selfassembly. Taken together, the results from the present study indicate that the cytoplasmic domain of gp41 by itself is sufficient to assemble into a multimeric structure. This finding supports the hypothesis that a multimeric form of the gp41 cytoplasmic domain plays a crucial role in virus infectivity.

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Infectious Mutants of HTLV-III with Changes in the 3′ Region and Markedly Reduced Cytopathic Effects

Cited by 225 publications

References 27 publications

Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages

Ordered appearance of human immunodeficiency virus type 1 nucleic acids following high multiplicity infection of macrophages

Incorporation of 12-methoxydodecanoate into the human immunodeficiency virus 1 gag polyprotein precursor inhibits its proteolytic processing and virus production in a chronically infected human lymphoid cell line.

Multimerization Potential of the Cytoplasmic Domain of the Human Immunodeficiency Virus Type 1 Transmembrane Glycoprotein gp41

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