The Exceptionally Large Genome of Hendra Virus: Support for Creation of a New Genus within the Family Paramyxoviridae

Abstract

An outbreak of acute respiratory disease in Hendra, a suburb of Brisbane, Australia, in September 1994 resulted in the deaths of 14 racing horses and a horse trainer. The causative agent was a new member of the family Paramyxoviridae. The virus was originally called Equine morbillivirus but was renamed Hendra virus (HeV) when molecular characterization highlighted differences between it and members of the genus Morbillivirus. Less than 5 years later, the closely related Nipah virus (NiV) emerged in Malaysia, spread rapidly through the pig population, and caused the deaths of over 100 people. We report the characterization of the HeV L gene and protein, the genome termini, and gene boundary sequences, thus completing the HeV genome sequence. In the highly conserved region of the L protein, the HeV sequence GDNE differs from the GDNQ found in almost all other nonsegmented negative-strand (NNS) RNA viruses. HeV has an absolutely conserved intergenic trinucleotide sequence, 3-GAA-5, and highly conserved transcription initiation and termination sequences similar to those of respiroviruses and morbilliviruses. The large genome size (18,234 nucleotides), the unique complementary genome terminal sequences of HeV, and the limited homology with other members of the Paramyxoviridae suggest that HeV, together with NiV, should be classified in a new genus in this family. The large genome of HeV also fills a gap in the spectrum of genome sizes observed with NNS RNA virus genomes. As such, it provides a further piece in the puzzle of NNS RNA virus evolution.

The Nipah Virus Fusion Protein Is Cleaved within the Endosomal Compartment

“…Because of the broad host range and the high mortality rates associated with infection, NiV has been classified as a biosafety level 4 agent. Because of their unique genetic and biological characteristics NiV and the closely related Hendra virus form a new genus, Henipavirus, within the Paramyxoviridae family (5,6).…”

Characterization of the Interactions between the Nucleoprotein and the Phosphoprotein of Henipavirus

“…Although the genome of HeV and NiV shares the same overall organization of members of the Paramyxovirinae subfamily, a few distinctive properties, including their much larger size, led to the creation of the Henipavirus genus to accommodate these newly emerged zoonotic viruses (2). Currently this genus contains two virus species and a number of strains isolated from humans, bats, horses, and pigs over a wide geographic area and during a period of 10 years.…”

The Central Role of the Matrix Protein in Nipah Virus Assembly and Morphogenesis

“…The contains the sequence GDNE rather than the highly conserved GDNQ motif found in all but three (subsequently discovered) non-segmented negative sense RNA viruses (37,50,135). The significance of this change is unknown.…”

“…Together, with Hendra virus (HeV), they are members of the recently created Henipavirus genus within the Paramyxoviridae family (135). The type species, HeV (81), appeared first in eastern Australia in 1994 and was transmitted to humans from infected horses [reviewed in (39) and (38)].…”