Identification of cellular genes affecting the infectivity of foot-and-mouth disease virus.
Foot-and-mouth disease virus (FMDV) produces one of the most infectious of all livestock diseases, causing extensive economic loss in areas of breakout. Like other viral pathogens, FMDV recruits proteins encoded by host cell genes to accomplish the entry, replication, and release of infectious viral particles. To identify such host-encoded proteins, we employed an antisense RNA strategy and a lentivirus-based library containing approximately 40,000 human expressed sequence tags (ESTs) to randomly inactivate chromosomal genes in a bovine kidney cell line (LF-BK) that is highly susceptible to FMDV infection and then isolated clones that survived multiple rounds of exposure to the virus. Here, we report the identification of ESTs whose expression in antisense orientation limited host cell killing by FMDV and restricted viral propagation. The role of one such EST, that of ectonucleoside triphosphate diphosphohydrolase 6 (NTPDase6; also known as CD39L2), a membrane-associated ectonucleoside triphosphate diphosphohydrolase that previously was not suspected of involvement in the propagation of viral pathogens and which we now show is required for normal synthesis of FMDV RNA and proteins, is described in this report.
Piccone
Maria E
ME
Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944, USA.
Feng
Yanan
Y
Chang
Annie C Y
AC
Mosseri
Ronen
R
Lu
Quan
Q
Kutish
Gerald F
GF
Lu
Zhiqiang
Z
Burrage
Thomas G
TG
Gooch
Christina
C
Rock
Daniel L
DL
Cohen
Stanley N
SN
D000818:Animals; D002417:Cattle; D002460:Cell Line; D020224:Expressed Sequence Tags; D005536:Foot-and-Mouth Disease / Q000235:genetics*; D029544:Foot-and-Mouth Disease Virus / Q000472:pathogenicity*; D015723:Gene Library; D006801:Humans; D011755:Pyrophosphatases / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics*; D012367:RNA, Viral / Q000378:metabolism
D016372:RNA, Antisense; D012367:RNA, Viral; D011755:Pyrophosphatases; C418082:nucleoside triphosphate diphosphohydrolase 6