       Document 0279
 DOCN  M9650279
 TI    A deletion in the proximal untranslated pX region of human T-cell
       leukemia virus type II decreases viral replication but not infectivity
       in vivo.
 DT    9605
 AU    Cockerell GL; Rovnak J; Green PL; Chen IS; Department of Pathology,
       College of Veterinary Medicine and; Biomedical Sciences, Colorado State
       University, Fort Collins; 80523-1671, USA.
 SO    Blood. 1996 Feb 1;87(3):1030-5. Unique Identifier : AIDSLINE
       MED/96151985
 AB    The function of untranslated (UT) nucleotide sequences in the proximal
       portion of the pX region of the human T-cell leukemia virus (HTLV)
       family of retroviruses remains enigmatic. Previous studies have shown
       that these sequences are not necessary for the expression of viral
       proteins or for the induction, transmission, or maintenance of the
       transformed cell type in vitro. To determine the effect of the UT region
       in vivo, separate groups of rabbits were inoculated with lethally
       irradiated, stable clones of the human B-lymphoblastoid cell line, 729,
       transfected with either a full-length wild-type HTLV-II clone (pH6neo)
       or a mutant clone containing a 324-bp deletion in the proximal UT
       portion of pX (pH6neo delta UT[6661-6984]), or nontransfected 729 cells.
       All rabbits inoculated with either wild-type or pX-deleted HTLV-II
       developed a similar profile and titer of serum antibodies against
       HTLV-II antigens, as determined by Western immunoblots, by 4 weeks
       postinoculation (PI). Antibody titers, as determined by enzyme
       immunoassay, were similar between the two groups of rabbits and
       increased over the 18-week period of study. All rabbits were killed at
       18 weeks PI, and spleen, peripheral blood lymphocytes (PBMC), bone
       marrow, and mesenteric lymph node were assayed for HTLV-II tax/rex
       sequences by quantitative polymerase chain reaction. Virus was detected
       in all tissues tested from all rabbits inoculated with 729pH6neo cells
       containing wild-type HTLV-II, which contained between 1.4 and 0.3 mean
       copies of provirus per cell. In contrast, the distribution and number of
       provirus copies were more limited in rabbits inoculated with 729pH6neo
       delta UT(6661-6984) cells containing UT-deleted HTLV-II; in most
       tissues, there was a fivefold to sevenfold reduction in mean provirus
       copies per cell as compared with rabbits inoculated with wild-type
       HTLV-II. All rabbits inoculated with control 729 cells remained negative
       for HTLV-II infection, as determined by the same techniques. It was
       concluded that UT sequences in the proximal portion of HTLV-II are not
       necessary for infection but confer increased replicative capacity in
       vivo.
 DE    Animal  B-Lymphocytes/TRANSPLANTATION/VIROLOGY  Clone
       Cells/TRANSPLANTATION/VIROLOGY  DNA, Viral/ANALYSIS  Female  *Genes, pX
       Human  HTLV-II/*GENETICS/IMMUNOLOGY/ISOLATION & PURIF/PHYSIOLOGY
       HTLV-II Antibodies/BIOSYNTHESIS  HTLV-II
       Infections/TRANSMISSION/VIROLOGY  Lymphoid Tissue/VIROLOGY  Male
       Polymerase Chain Reaction  Proviruses/ISOLATION & PURIF  Rabbits
       Regulatory Sequences, Nucleic Acid  Sequence Deletion  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  Transfection  Virus
       Replication/*GENETICS  JOURNAL ARTICLE

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

