A Comparative Assessment of the Pathogenic Potential of Newly Discovered Henipaviruses.

Recent advances in high-throughput sequencing technologies have led to the discovery of a plethora of previously unknown viruses in animal samples. Some of these newly detected viruses are closely related to human pathogens. A prime example are the henipaviruses. Both Nipah (NiV) and Hendra virus (HeV) cause severe disease in humans. Henipaviruses are of zoonotic origin, and animal hosts, including intermediate hosts, play a critical role in viral transmission to humans. The natural reservoir hosts of NiV and HeV seem to be restricted to a few fruit bat species of the Pteropus genus in distinct geographic areas. However, the recent discovery of novel henipa- and henipa-like viruses suggests that these viruses are far more widespread than was originally thought. To date, these new viruses have been found in a wide range of animal hosts, including bats, shrews, and rodents in Asia, Africa, Europe, and South America. Since these viruses are closely related to human pathogens, it is important to learn whether they pose a threat to human health. In this article, we summarize what is known about the newly discovered henipaviruses, highlight differences to NiV and HeV, and discuss their pathogenic potential.

Recombinant Soluble Henipavirus Glycoprotein Preparation.

Henipaviruses possess two envelope glycoproteins, the attachment (G) and the fusion (F) proteins that mediate cellular entry and are the major targets of virus-neutralizing antibody responses. Recombinant expression technologies have been used to produce soluble G and F proteins (sG and sF) that retain native-like oligomeric conformations and epitopes, which are advantageous for the development and characterization of vaccines and antiviral antibody therapeutics. In addition to Hendra virus and Nipah virus tetrameric sG and trimeric sF production, we also describe the expression and purification of Cedar virus tetrameric sG and Ghana virus trimeric sF glycoproteins. These henipavirus glycoproteins were also used as immunizing antigens to generate monoclonal antibodies, and binding was demonstrated with a pan-henipavirus multiplex microsphere immunoassay.

Paramyxoviruses in rodents: A review.

Paramyxoviruses have been shown to infect a wide range of hosts, including rodents, and humans. Several novel murine paramyxoviruses have been discovered in the last several decades. Although these viruses are unclassified, they are recognized as Beilong virus, Mojiang virus (MojV), and Tailam virus in rats, Jeilongvirus, Nariva, Paju Apodemus paramyxovirus-1 and -2 in mice, and Pentlands paramyxovirus-1, -2, and -3 in squirrels. These paramyxoviruses were reported mainly in China and a few other countries like Australia, the Republic of Korea, Trinidad, and France. In June 2012, it becomes a great concern in China whereby, three miners were reported dead potentially caused by a novel zoonotic MojV, a henipa-like virus isolated from tissue samples of rats from the same cave. Rats are considered to be natural hosts for the MojV from the literature research. The classified paramyxovirus, Sendai virus in rodents is also reviewed. Paramyxoviruses infection in rodents leads to respiratory distress such as necrotizing rhinitis, tracheitis, bronchiolitis, and interstitial pneumonia. Infections caused by paramyxoviruses often spread between species, manifesting disease in spillover hosts, including humans. This review focuses on the paramyxoviruses in rodents, including the epidemiological distributions, transmission and pathogenesis, clinical manifestations, diagnostic methods, and control and prevention of paramyxoviruses infection to provide a better understanding of these highly mutating viruses.

Functional Analysis of the Fusion and Attachment Glycoproteins of Mojiang Henipavirus.

Mojiang virus (MojV) is the first henipavirus identified in a rodent and known only by sequence data, whereas all other henipaviruses have been isolated from bats (Hendra virus, Nipah virus, Cedar virus) or discovered by sequence data from material of bat origin (Ghana virus). Ephrin-B2 and -B3 are entry receptors for Hendra and Nipah viruses, but Cedar virus can utilize human ephrin-B1, -B2, -A2 and -A5 and mouse ephrin-A1. However, the entry receptor for MojV remains unknown, and its species tropism is not well characterized. Here, we utilized recombinant full-length and soluble forms of the MojV fusion (F) and attachment (G) glycoproteins in membrane fusion and receptor tropism studies. MojV F and G were functionally competent and mediated cell-cell fusion in primate and rattine cells, albeit with low levels and slow fusion kinetics. Although a relative instability of the pre-fusion conformation of a soluble form of MojV F was observed, MojV F displayed significantly greater fusion activity when heterotypically paired with Ghana virus G. An exhaustive investigation of A- and B-class ephrins indicated that none serve as a primary receptor for MojV. The MojV cell fusion phenotype is therefore likely the result of receptor restriction rather than functional defects in recombinant MojV F and G glycoproteins.