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J Virol, May 1998, p. 3539-3546, Vol. 72, No. 5
Saint Louis University Health Sciences
Center, St. Louis, Missouri 63110,1 and
St. Jude Children's Research Hospital, Memphis, Tennessee
381052
Received 12 September 1997/Accepted 21 January 1998
The putative envelope glycoproteins of hepatitis C virus (HCV)
likely play an important role in the initiation of viral infection. Available information suggests that the genomic regions encoding the
putative envelope glycoproteins, when expressed as recombinant proteins
in mammalian cells, largely accumulate in the endoplasmic reticulum. In
this study, genomic regions which include the putative ectodomain of
the E1 (amino acids 174 to 359) and E2 (amino acids 371 to 742)
glycoproteins were appended to the transmembrane domain and cytoplasmic
tail of vesicular stomatitis virus (VSV) G protein. This provided a
membrane anchor signal and the VSV incorporation signal at the carboxy
termini of the E1 and E2 glycoproteins. The chimeric gene constructs
exhibited expression of the recombinant proteins on the cell surface in
a transient expression assay. When infected with a
temperature-sensitive VSV mutant (ts045) and grown at the
nonpermissive temperature (40.5°C), cells transiently expressing the
E1 or E2 chimeric glycoprotein generated VSV/HCV pseudotyped virus. The
resulting pseudotyped virus generated from E1 or E2 surprisingly
exhibited the ability to infect mammalian cells and sera derived from
chimpanzees immunized with the homologous HCV envelope glycoproteins
neutralized pseudotyped virus infectivity. Results from this study
suggested a potential functional role for both the E1 and E2
glycoproteins in the infectivity of VSV/HCV pseudotyped virus in
mammalian cells. These observations further suggest the importance of
using both viral glycoproteins in a candidate subunit vaccine and the
potential for using a VSV/HCV pseudotyped virus to determine HCV
neutralizing antibodies.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Functional Role of Hepatitis C Virus Chimeric
Glycoproteins in the Infectivity of Pseudotyped Virus

*
Corresponding author. Mailing address: Division of
Infectious Diseases and Immunology, Saint Louis University Health
Sciences Center, 3635 Vista Ave., St. Louis, MO 63110. Phone: (314)
577-8648. Fax: (314) 771-3816. E-mail:
rayr{at}wpogate.slu.edu.
Present address: Department of Infectious Diseases, Sahlgrenska
University Hospital, 416 85 Gothenburg, Sweden.
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