Sunday, April 21, 2013

Nipah Virus: a real life Contagion?

A newly emergent, deadly virus

            Throughout the last fifteen years, a highly fatal virus has emerged.  Since its first discovery in 1998, Nipah virus has infected nearly 500 people throughout Asia, and produced a mortality rate greater than 50% (1).  Nipah virus can be spread from either human-animal or human-human contact.  During the first outbreak of Nipah, transmission occurred primarily via respiratory droplets from infected pigs in Malaysia (2).  On the other hand, some of the outbreaks in India and Bangladesh were most likely due to contact with fruit bat saliva or urine (1).  In addition, some of the more recent cases of Nipah were transmitted directly from person to person, with many of the infections occurring in a hospital setting (1).  At first, Nipah virus symptoms resemble those of the flu, as many patients report headaches, muscle pains, vomiting, and a sore throat (1).  However, as the disease progresses, people experience encephalitis, and possible respiratory illness (1).  In serious cases, Nipah can lead to coma and death (1). There currently are no vaccines or treatment options for Nipah.

            Nipah virus is a member of the Paramyxoviridae family (2).  It is closely related to the Hendra virus, which causes similar respiratory and neurological symptoms (3).  Nipah virus is a (-) sense, single-stranded RNA virus that contains a nonsegmented genome (2).  Because Nipah is such a fatal virus, and there are no vaccines or treatment options available, there is little known about it.  All research involving Nipah must be completed at BSL-4 facilities containing the highest possible levels of security and safety.  Recently, researchers at the Institute of Virology, Philipps University of Marburg, Germany investigated how Nipah virus enters and exits an infected epithelial cell.   Although researchers have clinically proven that Nipah infects epithelial cells in the respiratory and urinal tracts, the mechanisms behind this are largely unknown.

Researching the unknown Nipah virus

            The first major objective of this study was to observe the mechanisms of Nipah virus (NiV) entry into a polarized epithelial cell.  To start, the researchers observed the distribution of the NiV entry receptors on the cells.  Specifically, they looked at the ephrin receptor expressions on polarized kidney epithelial cells (MDCK).  The researchers found an even distribution of ephrin throughout the apical and basolateral surfaces of the cell.  Then, MDCK cells were selectively infected to either the apical or basal filter chamber; and immunostained for presence of NiV in the cell.  As expected, NiV was able to infect the MDCK cells regardless of the surface domain.  Thus, NiV entry was found to be bipolar.

            Next, researchers investigated the release of NiV.  Although NiV entry appears to be bipolar, egress predominantly occurs via apical surfaces.  At 48 hours past infection, over 98% of the released infectious particles were found in the apical chamber filter.  Additionally, researchers compared the envelope glycoprotein expressions on apical and basal surfaces.  NiV contains three glycoproteins: F, G, and M.  Researchers discovered that all three of these proteins were found much more on the apical surface of the cell than the basolateral surface, thus complementing the previous egress data.  Additionally, although NiV usually exits the cell through the apical surface, at a high multiplicity of infection, it can disrupt the integrity of the MDCK cells.  Thus, through this disruption, NiV can overcome the epithelial barrier, and reach the basolateral side.

Why is this data important?

            Viral entry and egress of epithelial cells is crucial because many mammalian viruses typically gain entry into their hosts through epithelial barriers.  Due to the bipolar nature of NiV entry, an infection efficiently establishes itself in either the apical or basal side of the upper respiratory tract, quickly spreads to cells around it, and sheds itself through mucosal surfaces.  Then, the virus can overwhelm its surroundings and disrupt any sort of polarity.

            The mechanisms of entry and exit are essential to the understandings of Nipah virus.  Currently, there are no vaccines or therapies for NiV.  However, as scientists discover more about how NiV undergoes viral replication, it will be easier to develop antiviral drugs or vaccines. 

            Now that researchers have found a possible mechanism for NiV entry and egress in epithelial cells, there are many future options available.  NiV is a very new and emergent infection, thus it is critical to gather as much data as possible regarding its replication cycle.  As soon as entry and exit are more thoroughly understood, it is necessary to explore some of the other aspects of NiV, such as cytoplasm transport.  Although Nipah is a dangerous, emerging virus, it is certainly possible to prevent any future outbreaks.

Primary Article:
Lamp B, Dietzel E, Kolesnikova L, Sauerhering L, Erbar S, Weingartl H, Maisner A. 2013. Nipah Virus Entry and Egress from Polarized Epithelial Cells. Journal of Virology 87 (6): 3143-3154.
Secondary Articles:
1. World Health Organization. 2009. Nipah Virus. http://www.who.int/mediacentre/factsheets/fs262/en/ Fact Sheet number 262.
2. Chua KB, Bellini WJ, Rota PA, Harcourt BH, Tamin A, Lam SK, Ksiazek TG, Rollin PE, Zaki SR, Shieh W, Goldsmith CS, Gubler DJ, Roehrig JT, Eaton B, Gould AR, Olson J, Field H, Daniels P, Ling AE, Peters CJ, Anderson LJ, Mahy BW. 20002. Nipah virus: a recently emergent deadly paramyxovirus. Science 288: 1432-1435.
3. World Health Organization. 2009. Hendra Virus. http://www.who.int/mediacentre/factsheets/fs329/en/ Fact Sheet number 329.
Contagion movie poster, Warner Brother Pictures. http://tusb.stanford.edu/2011/10/page/2 This image is of low resolution and thus is not copyrighted.

1 comment:

  1. With so few people per year having gotten sick because of this virus, it's good that it's at least not an epidemic at this point. I would be interested to see how easily this virus is spread; if there's a potential for it to become widespread and infect people in a few continents, then the virus could indeed cause an epidemic. Although there are no treatment options currently, it's comforting that at least some information about the virus has been found.