Henipaviruses: recent observations on regulation of transcription and the nature of the cell receptor.
Hendra virus (HENV) and Nipah virus (NIPV) are classified in the new genus Henipavirus, within the subfamily Paramyxovirinae, family Paramyxoviridae. The genetic and biological characteristics that differentiate henipaviruses from other members of the subfamily are summarized. Although they do not display neuraminidase and hemagglutination activities and in that regard resemble viruses in the genus Morbillivirus, several recent observations highlight similarities between henipaviruses and respiroviruses (genus Respirovirus) in structure and replication strategy. First, three-dimensional modeling studies suggest that the external globular head domain of the HENV G protein resembles that of respiroviruses rather than morbilliviruses. Second, the pattern of transcriptional attenuation in HENV-infected cells resembles that observed with Sendai virus, a respirovirus, and differs from that found in cells infected with measles virus, a morbillivirus. Henipaviruses have a broad host range in vitro and in vivo, indicating wide distribution of cellular receptor molecules. The extensive host range has been confirmed in a quantitative in vitro cell-fusion assay using recombinant vaccinia viruses expressing the attachment and fusion proteins of HENV and NIPV. Cell lines of diverse origin and which are permissive in the in vitro cell fusion assay have been identified and the pattern of relative susceptibilities is the same for both HENV and NIPV, implying that both viruses use the same cell receptor. Protease treatment of permissive cells destroys their ability to fuse with cells expressing viral envelope glycoproteins. Virus overlay protein binding assay (VOPBA) and radio-immune precipitation assays confirm that both HENV and NIPV bind to membrane proteins in the 35-50 kD range. Treatment of cell membrane proteins with N-glycosidase eliminates HeV binding activity in VOPBA whereas treatment with neuraminidase has no effect on binding. Thus preliminary evidence suggests that NIPV and HENV bind to the same glycoprotein receptor via a non-sialic acid-dependant mechanism.
Eaton
B T
BT
Australian Animal Health Laboratory, CSIRO Livestock Industries, Geelong, Australia. Bryan.eaton@csiro.au
Wright
P J
PJ
Wang
L F
LF
Sergeyev
O
O
Michalski
W P
WP
Bossart
K N
KN
Broder
C C
CC
D003937:Diagnosis, Differential; D045403:Henipavirus / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D045464:Henipavirus Infections / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D011991:Receptors, Virus / Q000502:physiology*; D014158:Transcription, Genetic
D011991:Receptors, Virus