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M9640568.TXT
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1996-03-04
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Document 0568
DOCN M9640568
TI Influence of ORF2 on host cell tropism of feline immunodeficiency virus.
DT 9604
AU Waters AK; De Parseval AP; Lerner DL; Neil JC; Thompson FJ; Elder JH;
Department of Molecular Biology, Scripps Research Institute, La; Jolla,
California 92037, USA.
SO Virology. 1996 Jan 1;215(1):10-6. Unique Identifier : AIDSLINE
MED/96146738
AB Feline immunodeficiency virus (FIV) is a lentivirus associated with an
immunodeficiency syndrome of the domestic cat. A short open reading
frame (ORF2), of unknown function, is present in all FIV isolates. We
have investigated the role of ORF2 in determining the cell tropism of
two infectious molecular clones of FIV. FIV-PPR is able to productively
infect feline peripheral blood leukocytes (PBLs) and a T lymphocyte cell
line (MCH5-4), but not a feline astrocyte cell line (G355-5) or Crandell
feline kidney cells (CrFK). In contrast, FIV-34TF10 is able to
productively infect G355-5 and CrFK cells, but not PBLs or MCH5-4 cells.
The major difference in these FIV clones is that ORF2 in FIV-PPR is
capable of encoding a 79-amino-acid peptide, whereas there is a stop
codon in ORF2 after 43 amino acids in FIV-34TF10. We performed
site-directed mutagenesis to change the stop codon (TGA) in FIV-34TF10
to a tryptophan (TGG), the amino acid present at this location in
FIV-PPR. FIV-34TF10 with ORF2 repaired (FIV-ORF2rep) productively
infected PBLs, MCH5-4 cells, and primary macrophages, as well as CrFK
and G355-5 cells, indicating that a protein encoded by ORF2 plays a role
in determining the host cell tropism of FIV. ORF2 contains hydrophobic,
acidic, and leucine-rich domains similar to those shown to be important
for transactivating proteins of other lentiviruses. Coexpression of a
plasmid expressing the ORF2 gene product with another construct
expressing the chloramphenicol acetyl transferase (CAT) gene driven by
the FIV LTR, resulted in transactivation of CAT expression in both
feline and human cells.
DE Amino Acid Sequence Animal Base Sequence Cats Cells, Cultured DNA,
Viral/GENETICS Human Immunodeficiency Virus, Feline/CHEMISTRY/*GROWTH
& DEVELOPMENT/ GENETICS/ISOLATION & PURIF Molecular Sequence Data
Mutagenesis, Site-Directed Open Reading Frames Structure-Activity
Relationship Support, U.S. Gov't, P.H.S. Trans-Activation (Genetics)
Transfection Viral Proteins/CHEMISTRY/*PHYSIOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).