Imagine an organism that cannot live on its own. It needs to have a host to replicate and carry out its life processes. After using the host, this parasite kills it. Sounds creepy? That’s exactly what viruses do. They are infectious agents that enter the cells and utilize the host cellular processes for their own benefit, like an unwanted house-guest. They hijack the host metabolic pathways for their survival and multiplication. Alternatively, they can remain latent for several generations, reactivating later to cause chronic infection and/or cell death. The mechanism of cell death can be quite gruesome: it can be explosive where a breakdown of the outer covering of cells cause them to lyse (cell lysis) and die or follow another route where cells essentially commit suicide to save non-infected cells (apoptosis).
Viruses are extremely diverse in their genetic make-up, the way they replicate and cause infections. Additionally, viruses can quickly accumulate several mutations resulting in viral offspring that are completely different from the parent virus. Therefore, it becomes a Herculean task to design vaccines or treatment procedures that can target viruses. However, not all viruses are evil. There are several studies that demonstrate how viruses can help fend off infections and help us stay healthy. Considering the wide variety of viruses, the hosts they infect, coupled with their inability to grow outside a host cell, the story of how they were discovered is especially intriguing.
The earliest studies of viruses can be traced back to Adolf Mayer, a German chemist. Adolf was studying an unusual disease in 1876 that affected tobacco plants, leaving the leaves with a mosaic pattern. In his studies, he had discovered that the sap from a diseased plant could be used to infect a healthy plant. At first, he had assumed that bacteria were responsible and so he tried to filter them out of the sap. When the filters didn’t work, he concluded that the disease was caused by smaller bacteria or toxins.
Mayer’s observations were reproduced in 1892 and 1898 by Dimitri Ivanovsky, a Russian botanist, and Martinus Beijerinck, a Dutch botanist. Although Ivanovsky did not pursue the matter further, Beijerinck believed that he had found a new infectious agent and named it a “soluble living germ“. He also reintroduced the name “virus”, which was originally coined in 1398 from the Latin name for poison.
In 1935, Wendell Meredith Stanley, an American biochemist was able to isolate tobacco mosaic virus (TMV) crystals. He was the first person to do so and showed that they remained active even after crystallization. His techniques enabled the characterization of other viruses, resulting in the understanding of several diseases such as yellow fever, polio, and influenza.
Wendell M Stanley (left) and bottle with a suspension containing paracrystals of TMV, isolated in 1935. Stanley later received the Nobel Prize in Chemistry in 1946, along with James Sumner and John Northrop, for their studies on the purification and crystallization of viruses. Source.
How do viruses multiply in living cells? They first attach to cell-surface of the host. Viruses can then enter the host in different ways: by injecting their genetic material into the cell or getting eaten up entirely by the cell. In the latter case, the viruses are stripped off their protein coat and their genetic material is released into the cell. The virus can now use the host cell machinery to produce viral proteins, which are then assembled to make complete viruses. These completed viruses are released either by rupturing the cell membrane.
The outcome of a viral infection depends on whether the host has encountered the virus previously, which host cells are targeted, and how strong the host immune system is. Vaccines such as MMR and flu shots can help expose the host to the virus in a controlled manner. When host is subsequently exposed to infectious doses of the virus, it can mount a stronger immune response. Interestingly, some viruses, such as the influenza virus, can undergo mutations at a faster rate in order to evade the immune system. This is why new versions of the flu shot are developed twice a year. Different viruses target different host cells: influenza virus infects the respiratory tract, hepatitis viruses attacks the liver, poliovirus destroys motor neurons in the central nervous system. When viruses target these cells, the body mounts several defensive strategies which include fever, rash, and inflammation. Furthermore, due to the nature of virus replication, they can damage the host cells leading to devastating consequences. For example, infection by HIV destroys several types of immune cells, and when these cell numbers fall below a critical level, the individual becomes susceptible to a wide range of infections.
HIV infection in cell: (1) HIV docking on to cell surface (2) Internalization of the capsid (3) The genetic material (RNA) inside the cell cytoplasm, surrounded by the capsid. RNA gives rise to DNA (red thread) using the host cellular machinery (4) DNA trying to breach the cytoplasmic-nuclear barrier (5) DNA entering through nuclear protein pore (6) The viral DNA wrapped around histone covered cellular DNA transcribing RNA (7) These RNAs organize and are covered by nascent capsid proteins (8) The nascent viral particles exit out of the nucleus into the cytoplasm (9) Mature virus leaves the cell either by exocytosis or by destroying it.
Although viruses can be deadly, not all viruses are bad. There is a growing body of evidence that suggests that viruses play a crucial role in maintaining gut microflora. For example, viruses that line the mucous membrane in the gut of several bacterial hosts, form the first line of defense against invading bacteria. Another example is the hepatitis G virus which neither benefits nor harms healthy humans. However, the same virus in HIV-positive patients slows down the progression of the disease by several mechanisms including through the reduction of the HIV replication process. The human gut is rich in viruses whose identities and functions are still being discovered. Amazingly, 8% of our genes contain viral genetic material, the incorporation of which has taken millions of years. Although the biological significance of most of these viral genes is unknown, studies have shown that at least some of them encode proteins that are essential for placental development.
So how did viruses come to be? Tracing their origins is difficult for several reasons: they don’t form fossils, they can insert their own genes into the organism they’re invading- making it difficult to differentiate the host genes from viral ones, and they can infect all organisms. Although there are several hypotheses, none of them can satisfactorily explain the origin of all viruses. The first hypothesis, known as ‘the progressive hypothesis’, is that viruses have originated from mobile elements. These elements could have utilized some structural proteins to envelop themselves thereby allowing them to move from one cell to another. The second hypothesis, the ‘regressive hypothesis’, states the opposite- viruses were initially complex organisms, which gradually lost their genetic information, resulting in the formation of a parasite that contained the bare minimum information required to cause an infection. The third hypothesis, also known as the ‘virus-first hypothesis’, states that viruses existed before cellular life, they were the first replicating entities and gradually became more complex to give rise to their present form as we know it.
Author:
Ananya Sen is currently a Ph.D. student in Microbiology at the University of Illinois at Urbana-Champaign. When she’s not studying oxidative stress, she is busy pursuing her passion for scientific writing. Currently, she contributes articles to ASM, ScienceSeeker, and her own blog where she discusses the history of various scientific processes. She is an ardent reader and will happily discuss anything from Jane Austen to Gillian Flynn. Her graduation goals include covering all the national parks in the U.S. with her sidekick Oscar, a Schnauzer/Pomeranian mix.
Illustrator:
Arghya Manna is a comics artist, illustrator, and a Ph.D. dropout. He began his career as a doctoral student at Bose Institute, India. He had been working on Tumor Cell migration in a 3D environment. Along with this, he was an active participant in several projects related to tumor immunology and cancer stem cell. After leaving the lab without bagging the degree Arghya found refuge in art and got involved in drawing comics. He is an enthusiast in History of Science and has been running a blog named “Drawing History of Science”. Arghya wishes to engage the readers of history and science with the amalgamation of images and texts.
Editors:
Roopsha Sengupta and Paurvi Shinde
Paurvi Shinde d
id her Ph.D. in Immunology from the University of Connecticut Health. She currently works as a Post Doc Fellow at Fred Hutchinson Cancer Research Center, where she studies the role of immune cells in providing protection against HSV-2 infection. Apart from research, she loves editing articles, listening to podcasts, dancing and hiking in the beautiful Pacific Northwest. Follow her on Linkedin.
Roopsha Sengupta is the Editor-in-Chief at ClubSciWri. She did her Ph.D. at the Institute of Molecular Pathology, Vienna and postdoctoral research at the Gurdon Institute, University of Cambridge, UK, specializing in the field of Epigenetics. During her research, she was involved in many exciting discoveries and had the privilege of working and collaborating with a number of inspiring scientists. As an editor for ClubSciWri, she loves working on a wide range of topics and presenting articles coherently, while nudging authors to give their best.
Blog design: Roopsha Sengupta
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