Showing posts with label virology. Show all posts
Showing posts with label virology. Show all posts

Wednesday, February 3, 2016

Where Do “New” Viruses Come From?


Every year there seems to be a new virus that just popped up out of nowhere to cause us a great deal of pain and suffering. Is it the work of a mad scientist vying for global domination? Are these viruses coming back to life after being frozen for millennia? Are they hitching a ride to Earth via meteorites?

The truth is many of these viruses are not so new – but we are creating new opportunities for them to infect us. Many viruses jump from other animals into people – a process known as “zoonotic transmission” – and some of our actions roll out the red carpet for the virus. Let’s take a closer look at where some of these “new” viruses may have originated and how they spiral out of control.

Zika

Microcephaly is a term used to describe babies born with much smaller head size than normal, which is indicative of incomplete brain development. In Brazil, this birth defect occurs about 150 times per year. However, in the past 4 months, nearly 4,000 babies have been born with microcephaly - a dramatic spike that has set off alarm bells.

Photo of a child born with microcephaly, which has been linked to the Zika virus.
While evidence is still circumstantial, the primary culprit is a previously obscure virus called Zika, named after the forest in Uganda where it was first identified in a rhesus monkey back in 1947. Zika is transmitted through mosquitoes, which basically operate like flying dirty syringes. If they fed on an infected person, they can transmit the virus to the next person they bite.

Global warming and increased travel have conspired to create excellent opportunities for viruses like Zika to spread. It only takes one infected person to attend a major spectacle (for example, the 2014 FIFA World Cup in Brazil) to start a chain reaction of viral transmission. Viruses need no passports and can jet set around the world in unprecedented time. Global warming is an issue because it has allowed the species of mosquito that carries these viruses to thrive in areas that used to be too cold. Even El Niño has been catching some of the blame for helping to spread Zika.

Ebola

While Zika jumped to humans from other primates, the African filovirus Ebola is thought to have originated in fruit bats. Bats can transmit a number of other deadly viruses, including rabies. Bats happen to be a source of food in several of the areas where Ebola outbreaks have occurred, consistent with the idea that bats are the culprits. Once Ebola infects a human, it can spread quite easily to other people through bodily fluids.

Bats like this one are now considered to be a major carrier capable of spreading the Ebola virus to people.
Ebola first appeared in humans in 1976 in the Sudan and the Democratic Republic of Congo. The initial outbreak killed an estimated 600 people, but the latest outbreak that began in 2014 in West Africa has been the worst in history, killing over 11,000 people. This wasn’t due to an enormous fruit bat invasion, but rather human-to-human transmission. Genetic studies indicated that the entire epidemic likely stemmed from just a single infected child in Guinea, the so-called “Patient Zero”. A catastrophic mix of poor health facilities and unsanitary practices ignited to spread the virus like wildfire.


The 2014 Ebola outbreak started with a toddler who fell sick in Meliandou village in Guinea. Source.
Credit: Live Science
MERS

MERS, Middle East Respiratory Syndrome, first made headlines in 2012. This life-threatening respiratory virus reared its ugly head in Saudi Arabia first, but has since been reported in 25 other countries, including those not in the Middle East (due to unwitting travelers carrying more than their luggage). MERS is caused by a coronavirus, so the causative agent is typically referred to as MERS-CoV. Like many other respiratory viruses, coughing in close proximity can spread MERS-CoV between people.

But how did MERS-CoV get into people in the first place? According to the World Health Organization:  “It is believed that humans can be infected through direct or indirect contact with infected dromedary camels in the Middle East. Strains of MERS-CoV have been identified in camels in several countries, including Egypt, Oman, Qatar and Saudi Arabia.”

It is easy to understand the respect and admiration one can have for a noble creature like the camel. But getting a little too intimate with a camel may literally leave you breathless.
So stay away from coughing camels! In some areas, camels are butchered for food and their milk and urine (yes, urine) is consumed. These practices provide additional avenues for possible transmission of MERS-CoV to humans.


UPDATE (3/1/16): A new study suggests that we have bats to thank once again for spreading MERS-CoV to camels.

HIV

Human Immunodeficiency Virus (HIV), which causes AIDS, wasn’t on anyone’s radar until an unusually large number of people starting suffering from rare diseases with strange names like Kaposi’s sarcoma, toxoplasmosis, and pneumocystis. These diseases are hardly ever seen in people with normal, healthy immune systems. Turns out they were secondary infections – the primary infection was HIV, which was destroying the very immune cells that are needed to keep those other illnesses at bay.

Historical records have placed the earliest cases of HIV infection to the 1950s, which suggests it has been moving through humans slowly through the decades prior to its explosion in the early 1980s. An increase in international travel, unsafe sexual practices, and intravenous drug use are all factors that have contributed to accelerating the epidemic.

HIV (yellow particles) is a cunning foe that destroys the immune cells (blue) designed to protect us from foreign invaders.
We still don’t know how HIV leapt into the fabric of human DNA, but the evidence is very strong that it came from other primates. SIV, or simian immunodeficiency virus, has been found in African primates and is highly similar to HIV; it is easy to imagine that blood from infected primates, some of which are butchered for food or kept as pets, found its way into a person's open wound. Once in humans SIV evolved into HIV, transmissible to others through bodily fluids. HIV likely spread around Africa in its early days through the use of shared needles in impoverished hospitals.

It’s a virus world after all

As you can see from these examples, many “new” viruses were actually pre-existing in other animals and just made a “species jump” into humans. But how did these viruses get into the other animals in the first place? That question is a lot harder to answer.

Viruses are little more than a fragment of DNA or RNA, perhaps rogue genes that escaped a cell and became independent, infecting other cells in order to replicate and spread. Richard Dawkins coined the term, “the selfish gene”, and that is a very accurate description of viral DNA/RNA. What we do know is that viruses have been around a long, long time, perhaps before the dawn of life itself. There are even viruses that infect bacteria.

Once inside host cells, viruses replicate quickly, which means they are very adaptable. Their ability to evolve quickly is likely to be a key factor explaining why these selfish genes can make a reproductive factory out of a wide variety of different hosts…and why “new” viruses can appear to spring out of nowhere.

While viruses are a nuisance to us now, they may have been important drivers of evolutionary change in the past. It has been proposed that RNA viruses may have led to the formation of DNA and DNA replication mechanisms, without which we would not even be here to complain about them!

Contributed by:  Bill Sullivan, Ph.D.

Simpson, D. (1964). Zika virus infection in man Transactions of the Royal Society of Tropical Medicine and Hygiene, 58 (4), 339-348 DOI: 10.1016/0035-9203(64)90201-9


Forterre P (2006). The origin of viruses and their possible roles in major evolutionary transitions. Virus research, 117 (1), 5-16 PMID: 16476498


Koonin EV, Senkevich TG, & Dolja VV (2006). The ancient Virus World and evolution of cells. Biology direct, 1 PMID: 16984643


Baize, S., Pannetier, D., Oestereich, L., Rieger, T., Koivogui, L., Magassouba, N., Soropogui, B., Sow, M., Keïta, S., De Clerck, H., Tiffany, A., Dominguez, G., Loua, M., Traoré, A., Kolié, M., Malano, E., Heleze, E., Bocquin, A., Mély, S., Raoul, H., Caro, V., Cadar, D., Gabriel, M., Pahlmann, M., Tappe, D., Schmidt-Chanasit, J., Impouma, B., Diallo, A., Formenty, P., Van Herp, M., & Günther, S. (2014). Emergence of Zaire Ebola Virus Disease in Guinea New England Journal of Medicine, 371 (15), 1418-1425 DOI: 10.1056/NEJMoa1404505

Thursday, September 24, 2015

Ice, Ice Baby: Bringing Frozen Viruses Back To “Life”

Back in 2003, a new class of giant, ancient viruses were found that preyed upon unsuspecting amoebas in the Paleolithic.  

Earlier this year, scientists published a study describing how they revived another one of these giant viruses, which has been frozen in Siberian permafrost for 30,000 years! We’ll discuss why they did this in a bit, but let’s first talk about how they did this.

Over the years, lots of cool stuff has been found well-preserved in ice. Otzi, a 5,000 year old “ice man” was a historic find in 1991. He went on to become a spokesperson for the GEICO auto insurance company.
Viruses are minute obligate intracellular parasites. In other words, they cannot replicate outside of a host cell, an attribute that gives them the unflattering distinction of being the worst houseguest ever. That’s right:  viruses storm into your home – unannounced – take off their coat and make themselves right at home. They ransack the place and raid your fridge without even asking. As if that wasn’t bad enough, you come home one day and catch the virus in the act of making babies – lots and lots of babies. Finally, this unruly family blows up your house as they leave, without so much as a “thank you”, and go on their merry way to invade other homes in your neighborhood.

While we can feel the pain that they cause, especially during cold and flu season, we can’t see the culprits. Viruses are really, really tiny - most are smaller than the molecular complex cells use to make proteins.
Many viruses are under 100 nM (0.1 micron), but some (like Ebola) are almost 1.0 micron. Compared to viruses, even a bacterium is enormous. 
So how does one find a virus in thousands of miles of ice? Virus hunters take an approach similar to finding a needle in a haystack. But in this case, instead of a magnet, the scientists use amoebas as “bait” to lure out viruses that might be chilling out in the permafrost.

Amoebas are single-celled organisms called protozoa that, like most cells, fall prey to viruses. By putting permafrost into amoeba cultures, scientists were able to screen samples for those that could kill the amoebas. And they found a “big” surprise.


Thick membrane or no, Pithovirus invades amoebas. Who knows…with this discovery, maybe scientists can devise a new treatment that targets the deadly brain-eating amoeba, Naegleria.
The virus spotted in these infected amoeba cultures resembled a so-called “pandoravirus” or “giant” virus. They are still microscopic of course, but considerably larger than the viruses we know of today (about 1.5 microns in length and 0.5 microns across). Not only are they larger in size, but they contain many more genes. By way of comparison, HIV contains less than 15 genes, but this giant virus has 500 genes. They christened this new giant virus “Pithovirus sibericum”, and it is the oldest virus ever to have been revived to date.

A “huge” find in the world of virology, Pithovirus is now growing in labs again after a 30,000 year slumber. Image taken from Legendre, et al.
Now why on earth would scientists bring a virus back from the dead? Are they mad? Are they trying to facilitate the apocalypse?

Of course not. As climate change continues to melt more and more ice, it is possible that these viruses are going to revive naturally. By resurrecting them in the lab in controlled conditions, researchers can get ahead of this curve by studying the virus. Study of the virus can help determine which one(s) pose a threat and, if so, vaccine and drug development efforts can get underway thanks to our knowledge of the virus. And don’t worry about Pithovirus – it was already found to be incapable of infecting animal cells.

Another reason these viruses are worthy of study is that they can reveal new insights into how cells evolved, since viruses can transfer their DNA to their hosts. They may even shed light on the greatest biological mystery:  the origin of DNA/RNA and how life came to be on Earth.

The same team of scientists isolated yet another ancient giant virus this year from the same permafrost and named it Mollivirus sibericum. You may also be wondering what Siberian virus hunters listen to while exploring those Hoth-like landscapes. I'll take a guess and hope that it is wrong...
 

Contributed by:  Bill Sullivan, Ph.D.
Follow Bill on Twitter.


Legendre, M., Lartigue, A., Bertaux, L., Jeudy, S., Bartoli, J., Lescot, M., Alempic, J., Ramus, C., Bruley, C., Labadie, K., Shmakova, L., Rivkina, E., Couté, Y., Abergel, C., & Claverie, J. (2015). In-depth study of , a new 30,000-y-old giant virus infecting Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1510795112
 
Legendre, M., Bartoli, J., Shmakova, L., Jeudy, S., Labadie, K., Adrait, A., Lescot, M., Poirot, O., Bertaux, L., Bruley, C., Coute, Y., Rivkina, E., Abergel, C., & Claverie, J. (2014). Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology Proceedings of the National Academy of Sciences, 111 (11), 4274-4279 DOI: 10.1073/pnas.1320670111