Virology 100x: Let’s start from the very beginning

Tobacco Mosaic Virus

The tobacco mosaic virus; the first virus discovered and studied.

Let me get one thing straight first – viruses are NOT the same thing as bacteria. They’re just not. Okay? Great.

What are viruses, then? Well, I could tell you that they’re nucleoprotein complexes that make use of cells to replicate; I could tell you that they are obligate intracellular parasites – that is to say, they’re obliged to be parasites inside our cells; I could even tell you that they do not undergo cell division. But I won’t.

Oh. I already did.

Never mind then.

The point is, viruses are all that and more. One of the most interesting things in the world, we still can’t decide if viruses are living organisms or not. They carry genetic material, and are able to replicate themselves (but only after they’ve infected a host cell). However, outside of cells, they become metabolically inert – they can’t make their own proteins or copy their own DNA (or in the cases of some cells, their own RNA). Yet they can ‘die’ – if they’re outside of their host cell for long enough, or are otherwise exposed to adverse conditions, they can no longer successfully infect cells. This straddling of the line between life and non-life is very likely to be a clue to how life originated; most viral genes are so unlike the genes of the rest of the planet that they may well have come from a common ancestor before cell-based life existed.

The core of any virus is its genetic material – either DNA or RNA; this may be wrapped up with viral proteins to form a nucleoprotein complex (from combining “nucle”ic acid + “protein”). Viral proteins are also incorporated into the protective coat surrounding the nucleoprotein complex to give rise to the basic viral particle (or the virion). Some viruses, particularly those that infect mammals, may also have an additional lipid envelope over its protective coat.

You may think that all viruses are harmful to us, but this is not true. Because of the proteins embedded in their protein coat (or lipid envelope), viruses are very specific about which species they will infect, much like how only one specific key can open one specific lock. In fact, there are viruses, known as bacteriophages, which are beneficial to us because they are able to infect, and thus cause the death of bacteria that are harmful to us. It has been suspected that some “healing waters” may have been effective due to the presence of viruses that infect pathogenic bacteria. Viruses also infect amoeba, fungi, plants, and of course, other animals. In fact, every species on Earth has a whole host of viruses that is specifically only able to infect that species.

lock and key

In this case, the pink object refers to a viral surface protein, while the orange object refers to a host cell surface protein/glycoprotein. Only when viral protein keys are able to fit into host protein/glycoprotein locks can the infection of a cell start to happen, so viruses are VERY specific about who they are able to infect.

The gold standard for determining a new virus is by cultivating and isolating the virus, and viewing it under an electron microscope. Unfortunately, this species specificity means that it is very difficult to cultivate human viruses in order to study them, because they won’t infect non-human cells. The best way to go about studying human viruses would of course be by infecting humans, but this is ethically problematic, to say the least. One partial solution would be to culture human cells in a dish, and throw some human viruses on top to infect the human cells. This helps with studying how viruses infect cells in the first place, and what effects they have on cells in isolation. However, viruses are very finicky, and it first takes a lot of trial and error, and later, precision and time, to properly grow them. This still doesn’t answer how viruses act in the whole body, though – especially in the presence of our immune system, which has been implicated in a large amount of the cellular damage it causes as it tries to rip the virus from our bodies. Scientists thus have to use genetically near-identical species such as monkeys, or modify mice and other model organisms such that they carry human proteins, and are then able to be infected by our human viruses.

Because viruses are basically protein coats around genetic material, they are therefore also ideal as a mechanism for transferring genes to our own genomes. These engineered viruses are known as viral vectors, and have been modified such that they no longer cause disease. Viral vectors have a wide range of applications, including gene therapy, cancer treatmentvaccine development, and even in basic neuroscience research. Virus-like particles, which are viruses emptied of their genetic material, are also being investigated for use in nanotechnology applications like drug delivery and diagnosis.

Ebola: From monkeys to us

Ebola is caused by a virus that causes viral hemorrhagic fever – that is to say, it results in fever and bleeding disorders, shock, and eventually, death. Other symptoms include edema, migraine, fatigue, vomiting, and diarrhea. Occurring most often in the African continent, ebolavirus outbreaks happen when the virus jumps from its animal reservoir to a human, thus spreading through the human population; however, it is still unknown which animal harbours ebolavirus, although a strong suspect is bats. Ebola

The first ebolavirus (EBOV) was isolated in 1976, in what was then known as Zaire (now called the Democratic Republic of the Congo), when it caused an outbreak in the local population, and was thus named the Zaire ebolavirus, or the Zaire virus. Almost simultaneously, a second species of ebola virus was isolated in Sudan, and thus was called Sudan ebolavirus (SUDV); at first it was thought to be of the same species as EBOV, but later studies proved it to be of a different species. Later, animal laboratory workers in Reston, Virginia, got a scare, when ebolavirus was identified in the sick primates that they had been handling. Luckily for them, this turned out to be an Asian species of ebolavirus that did not cause disease in humans. All in all, five genetically and immunologically distinct species of ebolavirus have been isolated, with each species having several different strains. The most virulent species is EBOV, or Zaire virus, with an average case fatality rate of approximately 83%, and there have been more outbreaks of EBOV than any other ebolavirus.

EBOV and its kin are RNA viruses that are unusually genetically stable, allowing researchers to determine that most outbreaks were caused by different strains of different species of ebolavirus, indicating that these outbreaks were probably from different viral reservoirs. Ebolaviruses are unusual in that they are one of the only species of filamentous animal viruses in the world; filamentous viruses are more usually found in plants, so it has been posited that ebolaviruses may have evolved from plant viruses. Ebolaviruses have an outer lipid envelope, which technically means that the virus can be disrupted via alcohol-based agents; however, very low levels of virions are needed for infection to occur in humans (in the range of 1-10 virions). As transmission from humans to humans is via contact with an infected person’s blood or other body fluids, practicing the barrier nursing (or these days, the standard precautions) method, involving the use of protective equipment such as gloves, masks, gowns and so on, is more effective and useful in preventing transmission.

An electron micrograph of an Ebola virus

An electron micrograph of an Ebola virus

It has been problematic to elucidate the mechanism of ebolavirus infection because of a lack of samples and the difficulty of culturing the virus in the laboratory. However, researchers finally figured out the structure of the EBOV glycoprotein (GP) as derived from a human survivor of an outbreak. EBOV GP is the only virally expressed protein on the surface of the virion; it is important in the replication cycle of EBOV because it is responsible for the attachment of the EBOV virion to host cells, as well as virion-cell membrane fusion. Hence, it is a vital target of vaccines against EBOV. Various types of vaccines, including live attenuated and DNA subunit vaccines, have been developed against EBOV, and thus far they have had some promising success in animal models such as mice, guinea pigs, and macaques.

EBOV and its kin primarily attack endothelial cells, white blood cells and red blood cells, and overwhelms the protein synthesis mechanism in these cells. It is also able to interfere with our adaptive immune system by inhibiting the activation of neutrophils, a type of white blood cell. After entering these cells, these viruses replicate in the cytoplasm, then cause the host cell to burst, spreading their virions even further throughout the body. When enough cells burst, this causes the patient’s organs to break down, and their blood to stop clotting, leading to death, if the virus is not expelled from the body by the immune system in time.

Unfortunately, there is no curative treatment available for ebolaviruses; there is only supportive treatment that helps to mitigate the symptoms. Although there is a promising drug target called Niemann–Pick C1(NPC) present in the cell membrane, which is important in helping EBOV bind to our cells, a drug that can successfully target NPC is still under development. Thus the best way to avoid being infected would be to avoid contact with bats or non-human primates, and to wear protective equipment when taking care of people who have been infected with ebolaviruses. Frighteningly, it seems that EBOV can be transmitted between species through the air via large droplets, although the range of such transmission is limited.



Ebola Virus

The Ebola Virus poster (Science Infographics 2011 Honorable Mention)

CDC | Ebola

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Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor

N Sullivan, Z-Y Yang, and G J Nabel Ebola Virus Pathogenesis: Implications for Vaccines and Therapies J. Virol Sept 2003 vol. 77 no. 18 9733-9737 doi: 10.1128/JVI.77.18.9733-9737.2003

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M McGrath Growing concerns over ‘in the air’ transmission of Ebola