Expression in
            <i>Escherichia coli</i>
            of Open Reading Frame Gene Segments of HTLV-III

Chang, Nancy; Chanda, Pranab K.; Barone, Anthony D.; McKinney, Sam; Rhodes, David; Tam, S. H.; Shearman, Clyde W.; Huang, Jianhe; Chang, Tse Wen; Gallo, Robert C.; Wong‐Staal, Flossie

doi:10.1126/science.2983429

Cited by 41 publications

(13 citation statements)

References 26 publications

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“…A number of investigators have either cloned and expressed or directly synthesized portions of the AIDS virus env protein and tested these fragments both for immunoreactivity with AIDS patient sera and for antigenicity (9,(34)(35)(36)(37). Sites on AIDS virus env that have been investigated by use of protein fragments are summarized in Fig.…”

mentioning

confidence: 99%

Sequence homology between acquired immunodeficiency syndrome virus envelope protein and interleukin 2.

Reiher¹,

Blalock²,

Brunck³

1986

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

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[9188][9189][9190][9191][9192], the authors request that the following be noted. The last paragraph on p. 9188 should read: "Others have obtained experimental evidence indicating that the region of IL-2 that contains peptide IL2-A is important for activity. Ju et al. (25) used site-directed mutagenesis to determine that residues 21-40 of IL-2 (residues 1-20 of the mature protein) form one of the regions of IL-2 required for full biological activity and that this region is recognized by neutralizing anti-IL-2 antibodies. Chizzonite et al. (24) Communicated by William A. Goddard III, August 8, 1986 ABSTRACT A region of homology has been found between the envelope (env) protein of the acquired immunodeficiency syndrome (AIDS) virus and a portion of interleukin 2 (IL-2) that purportedly binds to the IL-2 receptor. This homology, between two proteins associated with opposing biological functions, suggests possible mechanisms for the immunosuppressive activity of the AIDS virus. Two mechanisms are proposed in which the AIDS virus env protein interferes with IL-2 activity either directly or indirectly. A region of similarity to the purported IL-2 receptor binding site on IL-2 and AIDS virus env is present in the env proteins of other retroviruses associated with immunosuppression. A synthetic peptide vaccine for AIDS is suggested based on the IL-2 receptor binding sequence in AIDS virus env.

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mentioning

confidence: 99%

Sequence homology between acquired immunodeficiency syndrome virus envelope protein and interleukin 2.

Reiher¹,

Blalock²,

Brunck³

1986

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

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“…More important, nonspecific reactivities seen in non-HTLV-III-infected individuals are likely due to the heterogeneity of the preparations used for assay. This is particularly true for assays using either whole virus or Escherichia coli-derived recombinant products as the immunoadsorbents, with which the host cells' major histocompatibility antigens or endogenous bacterial proteins are frequently copurified (19,23). Since antibodies to these contaminating antigens are frequently found in normal individuals, false-positive results cannot be eliminated by using current antigen isolation processes.…”

Section: Methodsmentioning

confidence: 99%

“…Efforts employing recombinant DNA technology to identify HTLV-III antigenic peptides reactive with sera from AIDS and AIDS-related complex (ARC) patients and asymptomatic HTLV-III-infected individuals have also been undertaken by many investigators (19)(20)(21)(22)(23). Success has been obtained by this approach.…”

Section: Introductionmentioning

confidence: 99%

Detection of antibodies to human T-lymphotropic virus type III by using a synthetic peptide of 21 amino acid residues corresponding to a highly antigenic segment of gp41 envelope protein.

Wang¹,

Steel²,

Wisniewolski³

et al. 1986

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

161

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A peptide of 21 amino acids with the sequence Arg-Ile-Leu-Ala-Val-Glu-Arg-Tyr-Leu-Lys-Asp-Gln-GlnLeu-Leu-Gly-Ile-Trp-Gly-Cys-Ser encoded by a segment in the env gene of human T-lymphotropic virus type m (HTLV-Il), corresponding to amino acids 586-606 of the precursor envelope glycoprotein, has been synthesized by the Merrifield solid-phase method. Combined serological and chemical analyses of this peptide and related peptides have revealed the importance of certain amino acid residues in the antigenic determinant of the relevant peptide. Enzyme immunoassay (EIA) employing this peptide as an antigen adsorbent was shown to reproducibly detect antibodies in sera of patients with HTLV-II infection. This assay provided positive results with all sera that were reactive with gp4l envelope protein of HTLV-Ill in electrophoretic immunoblot analysis. Thus far, no false-positive sera have been encountered in control populations. Our EIA with this peptide as the coating antigen is shown to have advantages over that with the whole HTLV-llI virus as an immunoadsorbent.Since the identification of a human retrovirus, named human T-lymphotropic virus type III (HTLV-III), acquired immune deficiency syndrome (AIDS)-related virus (ARV), or lymphoadenopathy-associated virus (LAV) as the infectious agent for AIDS (1-4),t substantial progress has been made in the studies of the virus and in the development of diagnostic methods for the detection of HTLV-III infection. With the establishment of permissive T-cell lines for mass production of HTLV-III virus (1), it has been possible to elucidate the structure and gene organization of HTLV-III, to determine the complete nucleotide sequence of the HTLV-III genome (5-8), and to use heat-inactivated HTLV-III as the immunoadsorbent for detection of antibodies against HTLV-III in sera of patients with HTLV-III infection (9)(10)(11)(12)(13)(14)(15)(16)(17)(18).Efforts employing recombinant DNA technology to identify HTLV-III antigenic peptides reactive with sera from AIDS and AIDS-related complex (ARC) patients and asymptomatic HTLV-III-infected individuals have also been undertaken by many investigators (19)(20)(21)(22)(23). Success has been obtained by this approach. However, it has not been able to localize and identify the peptide sequences representing the antigenic epitope(s).Synthetic peptides are used increasingly to map antigenic or immunogenic sites on the surface of proteins and, in turn, as possible vaccines (reviewed in ref. 24). We have synthesized numerous peptides corresponding to various regions of envelope protein of HTLV-III and analyzed their reactivity with sera from AIDS patients. Our initial emphasis was on the gp4l glycoprotein, the transmembrane portion of envelope protein gp160, which has previously been identified as the antigen most consistently recognized by antibodies in patients with AIDS and ARC (25,26).In this paper, we report (i) the identification of a peptide 21 residues in length with the sequence Arg-Ile-Leu-Ala-ValGlu-Arg-Tyr-Leu-Lys-Asp-Gln-Gln-Le...

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“…Sera from AIDS patients react with peptides derived from orf [53], The env gene also differs from that of all other retroviruses, in that it has 20 possible glycosylalion sites.…”

Section: Retroviral Structure: Unique Aspects Of Human Retrovirusesmentioning

confidence: 99%

Immunopathology Associated with Human Lymphotropic Retroviruses

Ruscetti¹

1985

Pathol Immunopathol Res

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Expression in Escherichia coli of Open Reading Frame Gene Segments of HTLV-III

Cited by 41 publications

References 26 publications

Sequence homology between acquired immunodeficiency syndrome virus envelope protein and interleukin 2.

Sequence homology between acquired immunodeficiency syndrome virus envelope protein and interleukin 2.

Detection of antibodies to human T-lymphotropic virus type III by using a synthetic peptide of 21 amino acid residues corresponding to a highly antigenic segment of gp41 envelope protein.

Immunopathology Associated with Human Lymphotropic Retroviruses

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