       Document 0950
 DOCN  M9650950
 TI    Enhanced specificity of truncated transmembrane protein for serologic
       confirmation of human T-cell lymphotropic virus type 1 (HTLV-1) and
       HTLV-2 infections by western blot (immunoblot) assay containing
       recombinant envelope glycoproteins.
 DT    9505
 AU    Varma M; Rudolph DL; Knuchel M; Switzer WM; Hadlock KG; Velligan M; Chan
       L; Foung SK; Lal RB; Department of Pathology, Stanford University,
       California 94305,; USA.
 SO    J Clin Microbiol. 1995 Dec;33(12):3239-44. Unique Identifier : AIDSLINE
       MED/96156135
 AB    Immunoassays based on the highly immunogenic transmembrane protein of
       human T-cell lymphotropic virus type 1 (HTLV-1) (protein 21c) are
       capable of detecting antibodies in all individuals infected with HTLV-1
       and HTLV-2. However, because of antigenic mimicry with other cellular
       and viral proteins, such assays also have a large proportion of
       false-positive reactions. We have recently identified an immunodominant
       epitope, designated GD21-I located within amino acids 361 to 404 of the
       transmembrane protein, that appears to eliminate such false positivity.
       This recombinant GD21-I protein was used in conjunction with additional
       recombinant HTLV type-specific proteins and a whole virus lysate to
       develop a modified Western blot (immunoblot) assay (HTLV WB 2.4). The
       sensitivity and specificity of this assay were evaluated with 352
       specimens whose infection status was determined by PCR assay for the
       presence or absence of HTLV-1/2 proviral sequences. All HTLV-1-positive
       (n = 102) and HTLV-2-positive (n = 107) specimens reacted with GD21-1 in
       the HTLV WB 2.4 assay, yielding a test sensitivity of 100%. Furthermore,
       all specimens derived from individuals infected with different viral
       subtypes of HTLV-1 (Cosmopolitan, Japanese, and Melanesian) and HTLV-2
       (IIa0, a3, a4, IIb1, b4, and b5) reacted with GD21-I in the HTLV WB 2.4
       assay. More importantly, HTLV WB 2.4 analysis of 81 PCR-negative
       specimens, all of which reacted to recombinant protein 21e in the
       presence or absence of p24 and p19 reactivity in the standard WB assay,
       showed that only two specimens retained reactivity to GD21-I, yielding
       an improved test specificity for the transmembrane protein of 97.5%.
       None of 41 specimens with gag reactivity only or 21 HTLV-negative
       specimens demonstrated reactivity to GD21-I. In an analysis of
       additional specimens (n = 169) from different geographic areas for which
       PCR results were not available, a substantial increase in the
       specificity of GD21-I detection was demonstrated, with no effect on the
       sensitivity of GD21-I detection among specimens from seropositive
       donors. Thus, the highly sensitive, GD21-I-based HTLV WB 2.4 assay
       eliminates the majority of false-positive transmembrane results, thereby
       increasing the specificity for serologic confirmation of HTLV-1 and
       HTLV-2 infections.
 DE    Amino Acid Sequence  Blotting, Western/*METHODS/STATISTICS & NUMER DATA
       Comparative Study  False Positive Reactions  Gene Products,
       env/GENETICS/IMMUNOLOGY  Human  HTLV-I/GENETICS/IMMUNOLOGY  HTLV-I
       Antibodies/BLOOD  HTLV-I Infections/*DIAGNOSIS/IMMUNOLOGY/VIROLOGY
       HTLV-II/GENETICS/IMMUNOLOGY  HTLV-II Antibodies/BLOOD  HTLV-II
       Infections/*DIAGNOSIS/IMMUNOLOGY/VIROLOGY  Immunodominant
       Epitopes/GENETICS  Molecular Sequence Data  Polymerase Chain Reaction
       Recombinant Proteins/GENETICS/IMMUNOLOGY  Sensitivity and Specificity
       Sequence Homology, Amino Acid  Serodiagnosis/METHODS/STATISTICS & NUMER
       DATA  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

