Arch Virol (2003) 148: 659–675
The envelope glycoprotein of human endogenous retrovirus
HERV-W induces cellular resistance to spleen necrosis virus
V. G. Ponferrada
, B. S. Mauck
, and D. P. Wooley
Department of Biochemistry and Molecular Biology, Wright State University
School of Medicine, Dayton, Ohio, U.S.A.
Center for Retrovirus Research, The Ohio State University,
Columbus, Ohio, U.S.A.
Received September 9, 2002; accepted November 25, 2002
Published online February 17, 2003
Summary. Human endogenous retrovirus type W (HERV-W) envelope glyco-
protein (Env) has recently been reported to induce fusion in cells expressing
the RD-114 and type D retrovirus receptor (RDR) and to serve as a functional
retroviralenvelope protein. In this report, another biological function for HERV-W
was demonstrated by testing its ability to protect cells against retroviral infection.
Spleen necrosis virus (SNV), a gammaretrovirus was chosen for testing resistance
because it uses RDR to enter cells. An HERV-W Env expression plasmid was
transfected into canine osteosarcoma cells (D-17), which are permissive for SNV
infection. Cell fusion assays were performed to demonstrate biological function
of HERV-W Env in D-17 cells. The presence of HERV-W env sequences was con-
ﬁrmed in stably transfected cell clones by using polymerase chain reaction. Viral
infectivity assays were performed with SNV and amphotropic Murine leukemia
virus (MLV-A) pseudotyped vector viruses to measure titers in D-17 cells ex-
pressing HERV-W Env and in negative control cells. The HERV-W Env caused
fusion of D-17 cells in culture and greatly reduced infection by SNV vector virus.
A 1000- to 10,000-fold decrease in SNV infectivity was observed for D-17 cells
expressing HERV-W Env as compared to D-17 cells that were not expressing
HERV-W Env. In contrast, infection by MLV-A pseudotyped vector virus was not
signiﬁcantly reduced. Thus, HERV-W Env confers host cell resistance to infection
by SNV. This is the ﬁrst report of a human endogenous retrovirus gene product
blocking infection by any exogenous retrovirus.
Endogenous retrovirus (ERV) gene sequences comprise up to 8% of the human
genome [8, 22, 25] and are also found in the genomes of other mammals and