Ultrastructural morphology of Ebola virus
By Maria Victoria Gonzaga
The Ebola virus disease is caused by the four known viruses of the genus Ebolavirus: Bundibugyo ebolavirus, Sudan ebolavirus, Tai Forest ebolavirus, and Zaire ebolavirus (or simply, EBOV). Their natural host is the fruit bats, particularly the Hypsignathus monstrosus, Epomops franqueti and Myonycteris torquata, of the Pteropodidae family. The infective agent can be transmitted to other animals, e.g. chimpanzees, gorillas, monkeys, forest antelope, and porcupines. The virus may spread to humans through unprotected handling of bushmeat. Humans may then spread the virus to another human host through direct contact with the infective body fluids, blood, and secretions (through the mucous membranes and broken skin). Fomites, such as contaminated hospital needles, may also be a means of viral transmission. Humans and other primates serve not as reservoir hosts but as accidental hosts.1 EBOV is regarded as the most dangerous among the four. It was the one that caused the outbreak in the Democratic Republic of Congo in 1975 and in 1995. The ongoing (2014) Ebola outbreak is also caused by an EBOV strain. However, the World Health Organization (WHO) believes that the EBOV strain is different from and unrelated to the previous major Ebola outbreaks in the Democratic Republic of Congo. Accordingly, the index case and the 80 contacts revealed to have neither travel history to the affected countries in West Africa nor direct contact with locals infected by it.2
EBOV is one virulent pathogen in having successfully targeted the first line of immune defense, the neutrophils. Other major target cells include endothelial cells and hepatocytes. However, its capacity to evade immune detection by infecting and interfering with the antiviral defense system of neutrophils makes it one hard pathogen to beat. In a recent study reported by Amarasinghe et al., a map is shown how eVP24, an Ebola protein, binds to a host protein. The binding according to them countered the host protein’s ability to carry the immune signal into the nucleus that would have initiated antiviral defenses. Amarasinghe et al. stated that eVP24 specifically binds to the nonclassical nuclear localization signal binding site on karyopherin alpha 5 (KPNA5). KPNA5 is a member of the importin alpha protein family, which is involved in importing proteins into the nucleus. When bound to eVP24, KPNA5 would not be able to transport tyrosine-phosphorylated STAT1 (PY-STAT1) into the nucleus. Because of this, the interferon signaling is disrupted. They also found that while eVP24 selectively targeted PY-STAT1 nuclear import (thereby countering cell-intrinsic innate immunity) the transport of other cargo essential for viral replication remains unaffected.3 With this information, they hinted a new potential therapeutic target for
Ebola virus disease; one that involves eVP24.
The emergence of the Ebola virus disease is closely being monitored all over the world. That’s expected, knowing that the agent of this disease is downright deadly, with an up to 90% case fatality rate in records. Initially, a virus of the wild animals, the virus proved that it can make humans susceptible, too, as evidenced by the time it caused the first outbreak in the Democratic Republic of the Congo (formerly, Zaire) in 1976 where 280 of 318 people that contracted the disease died. Also in the same year, an outbreak occurred in Sudan killing 151 out of the 284 people affected. Containment efforts of the WHO (such as quarantining villagers and sterilizing medical equipment) were successful to stop the disease from further spreading. However, the next major outbreak occurred after nearly twenty years. In 1995, 315 cases in the Democratic Republic of Congo were reported; 254 of them died.1 And recently, an epidemic of the disease is again spreading. Believed to begin in Guinea in December 2013, the virus spread to other parts of West Africa, particularly in Liberia, Sierra Leone, Nigeria, and Senegal. The 2014 outbreak is profoundly monitored because it carries by far the highest record of reported cases and deaths in the history of the virus. On August 28, 2014, WHO together with the Ministries of Health in Guinea, Sierra Leone, Liberia, and Nigeria reported 3,069 (suspected and confirmed) cases of the disease. 1,752 were confirmed by laboratory testing whereas death count already reached 1,552.2 These reports are alarming since cases continue to increase and outnumbering the number of cases from previous outbreaks.
At present, there is no known cure or vaccine for Ebola virus disease. Nevertheless, research in this regard continues and strategies to prevent the spread of the lethal virus has become a worldwide effort.
1 Ebola virus disease. (2014). WHO. Retrieved August 29, 2014, from http://www.who.int/mediacentre/factsheet
2 Ebola virus disease update, West Africa – update 28 August 2014. (2014, August 28). – WHO. Retrieved August 31, 2014, from http://www.afro.who.int/en/clusters-a-programmes/dpc/epidemic-a-pandemic-alert-and-response/outbreak-news/4264-ebola-virus-disease-update-west-africa-28-august-2014.html
3 Wei Xu, Megan R. Edwards, Dominika M. Borek, Alicia R. Feagins, Anuradha Mittal, Joshua B. Alinger, Kayla N. Berry, Benjamin Yen, Jennifer Hamilton, Tom J. Brett, Rohit V. Pappu, Daisy W. Leung, Christopher F. Basler, Gaya K. Amarasinghe. Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1. Cell Host & Microbe, 2014; 16 (2): 187 DOI: 10.1016/j.chom.2014.07.008 http://www.cell.com/cell-host-microbe/abstract/S1931-3128(14)00263-7