How viruses multiply D. Indumathi, The Institute of Mathematical Sciences, Chennai Most bacterial diseases can be cured, usually by administering some form of anti-biotic. But viruses are different. Sometimes the disease caused by the virus gets better on its own, such as influenza (flu) or chicken-pox. Some viruses such as polio, ebola or human immuno-deficiency virus (HIV) are deadly and have no cure. The recent Covid-19 pandemic that has been caused by the SARS-coronavirus-2 is still raging across the world with no cure in sight. What makes viruses so different from bacteria? What is a Virus Unlike bacteria (or plants or animals), viruses are not cells and cannot replicate (multiply) on their own. In fact, they show characteristics of living and well as non-living things. So viruses have to rely on another organism for energy production and reproduction, in fact, for survival. Such organisms off which viruses live are called host organisms. Hosts can be plants, animals, or bacteria. When humans become the hosts, the entry and multiplication of viruses in our bodies leads to various diseases. When the virus lives off a bacteria, it is called a bacteriophage and is very useful in diagnosis and treatment of bacterial infections and to understand more about them. Such viruses, called retroviruses, replicate its genome using an enzyme called reverse transcriptase. They have the unique ability to insert genes into human chromosomes and are used in cloning and gene therapy to cure various diseases. Virus Structure Viruses are much smaller than bacteria and cannot be seen under a microscope. While bacteria (or cells) are microns in size (1 micron is 1 millionth of a meter, or 10^-6 m), viruses are only 0.02-0.4 microns in diameter. So it was hard to isolate them. The first virus to be studied was the virus that infects the tobacco plant, called tobacco mosaic virus, in the 1890s. The virus infects many other plants as well, and its infection causes leaves to show "mottled" appearance with patches on them (see picture). Only when the electron microscope was invented could viruses be seen and the full structure of the tobacco mosaic virus was determined by Rosalind Franklin in 1955. Viruses have very simple geometrical structure. They contain the genetic material (which may be DNA or RNA; see Box) surrounded by a protein coat called capsid. Some larger ones have an additional outer coat called an envelope. This is very important in determining how viruses infect host cells. Some viruses can remain dormant inside the host for many years, that is, without affecting the host. The HIV virus, for example, can remain dormant for even 10 years. At some point, caused by an unknown trigger, the virus becomes active and causes the disease. Box on DNA versus RNA DNA stands for de-oxy-ribo-nucleic acid while RNA stands for ribo-nucleic acid. They are very similar except that DNA is a double stranded molecule wrapped around in a helical structure like a plait with 2 legs while RNA is a single-stranded molecule. You may have heard that DNA contains the genetic code and is inside the nucleus of all living cells. RNA has a completely different function and is typically used to carry information from the DNA to the outside of the cell (called cytoplasm) to give instructions on making proteins. Human have 23 pairs of chromosomes. Actually, a chromosome is just a chain of DNA, which has been tightly coiled around proteins called histones and made compact so it fits inside the nucleus. Bits of DNA code for different proteins. These bits are called genes and their function is very specific; one gene produces or codes for only a specific protein. So, the function of DNA is to self-replicate and store genetic information, while that of RNA is to store information on proteins. End of BOX Envelope or not? All viruses have a protein coating or capsid, but some viruses, such as the flu virus, have an additional envelope made of lipids (fats). Viruses without this extra membrane are called naked viruses. The presence or absence of an envelope is an important determining factor in how a virus interacts with the host's membrane, how it enters a host, and how it exits the host after maturation. The novel SARS-Coronavirus-2, for instance, has an envelope. Viral replication Viral replication is how the virus multiplies in the human host cells during the infection process. The first thing to understand is that viruses cannot propagate through cell division, since they are a-cellular. So if there is a virus in the air around you, it simply stays there. It cannot do anything, until it enters a host or target cell. For instance, this may be your own (or any human) cell. Once it does this, it uses the machinery -- including the proteins, nucleic acid, and energy for the process -- of the host cell to replicate, or make copies of itself. Most DNA viruses assemble in the nucleus while most RNA viruses develop outside, in the cytoplasm. The virus attaches to the cell membrane of the host cell. It then injects its DNA or RNA into the host to initiate infection. Cell enzymes strip off the capsid or virus protein coat, thus exposing the DNA or RNA. The virus RNA produces messenger RNA (mRNA). The mRNA is used to instruct the host cell to make virus components. This is then used to make copies of itself, by putting the virus proteins and RNA/DNA together together in a sort of self-assembly process. What is formed is called a virion. It is simply an active or intact virus particle. This replication may take place in the cell's nucleus, cytoplasm or at plasma membrane for most developed viruses, but so far all these virus copies are still inside a host cell. In order to infect you, they have to be released from the cell. This is usually done by killing the cell by bursting its cell membrane and is called lysis. If the virus has an envelope, then the new virus copy first acquires the envelope and then leaves the host cell by budding (see figure). In this case the original cell does not die. However, many viruses, once they infect a cell, cause it to die eventually. In the case of the human papilloma virus (HPV), for instance, it causes cancer. Viruses multiply quickly because they have so few genes. The influenza (flu) virus has only 8 genes, and the rotavirus which causes diarrhoea in small children, has 11. Humans have more than 20,000 genes. How they were found Viruses were first isolated when electron microscopes were invented. The tobacco mosaic virus (which infected the tobacco plant) was first examined under the microscope and found to be made up of mostly protein. Later it was found to be made of protein and RNA. Can you think how they grew the virus in the lab? After all, viruses are not living things. We know that eggs are full of protein! In 1931, scientists Ernest Goodpasture and Alice Woodruff grew the influenza virus in chicken eggs. Today, more than 5000 different viruses have been found, in all corners of the Earth, and, as we know, we are finding new ones all the time, like the SARS-Cov-2 virus. Infection from viruses Viruses are the cause of many human diseases including influenza, chickenpox, and the common cold. They can also remain dormant (quiet, not doing anything) in the host for a long time. For instance, the Human Immunodeficiency virus (HIV) can remain dormant for ten years. Influenza viruses The common cold is caused by the rhino virus, while influenza or flu is caused by the influenza virus. There are four types of influenza virus, of which types A, B, and C can infect humans. While type D infects pigs and cattle, they have not yet infected humans. Of the remaining three, types B and C are rare. You may have heard of some of the type A viruses, such as H1N1 (causes swine flu) and H5N1 (causes bird flu) which have already caused a lot of disease in the world over the years. The flu viruses have an envelope and are transmitted by the infected person sneezing and coughing, just like with the corona viruses. Rhinoviruses do not have an envelope and are really small, about 0.03 microns, while flu viruses are about 0.1 microns. You may have seen pictures of the corona virus, with the "spikes". These are actually proteins, and the influenza virus has them too. Corona viruses These are also enveloped viruses, like flu viruses and also cause respiratory tract infections similar to common cold and influenza. In fact, it is very difficult to tell which virus you have! There are many types of corona viruses, and some of them (human coronavirus 229E and OC43) just give you a common cold. Some of them are more deadly and you may have heard of them: SARS-Cov (identified 2003), MERS-Cov (2012), and SARS-Cov-2 (2019). All are similar in size to the influenza virus, and also have the spike proteins that give the viruses their name (corona means crown). All of them involve respiratory tract infections, and hence the name SARS: Severe Acute Respiratory Syndrome or SARS. (MERS stands for Middle-East Respiratory Syndrome and was so called because it was identified in Saudi Arabia in 2012 and then spread across the middle eastern countries. The infection was passed by camels to humans. This was a deadly disease but was brought under control mainly because it did not spread directly from humans to humans. History repeats The SARS-Cov pandemic began in Nov 2002, and ended by the end of Jun, 2003. By this time, more than 8000 people from various countries across the world were infected and 774 died, including the Italian doctor, Dr Carlo Urbani, who first identified that it was a new virus and a new disease. He reported it to the World Health Organisation (WHO) and also recommended isolation and screening measures for travelers, thus slowing the spread of the disease. SARS-Cov was passed by bats to humans, and then from human to human. Hence it was more of a danger, although the death rate (mortality) was much lower than MERS. However, the virus spread was controlled by isolation and quarantine. Preventive measures included handwashing well with soap and water, cleaning surfaces regularly and disinfecting them, and other simple basic hygiene measures. In short, everything that is being recommended for SARS-Cov-2 was also tried successfully for SARS-Cov in 2003! There is still no cure for either SARS-Cov disease. Only isolation, testing, and physical distancing seem to work to control the spread of this disease. SARS-Cov-2 and Covid-19 The SARS-Cov-2 coronavirus is similar to the SARS-Cov virus and causes the Covid-19 (corona virus disease 2019) disease. It is also found in bats. However, it appears to be much more infectious than SARS-Cov. The disease is spread mainly by breathing in droplets from infected persons who are coughing and sneezing. The main difference between this and SARS-Cov is that the infected person is himself infectious much before he shows symptoms, which can take 2-14 days. So it is possible that this person can infect many others before he is isolated. In contrast people sick with SARS-Cov became infectious only a few days after they showed symptoms, so it was easier to isolate them and prevent the disease from spreading. The viral load in an infectious person is the amunt of virus that the person has in his mucous or other body fluids. This load is largest in the earliest time of the SARS-Cov-2 infection, and then decreases over time. Again, this makes the person who has just caught the disease extremely infectious. What to expect if you are sick The virus appears to be mostly transmitted through coughing when small water droplets carrying viral load is sent into the air which others later inhale (see picture). It is possible that the virus is also expelled from the air that is exhaled while breathing while this is not clear as yet. Viruses have been detected in stools (faeces) of patients but not in urine; again it is not considered a significant source of infection. Most people have mild symptoms of fever, dry cough and tiredness. This begins 2-14 days after being infected. These mild symptoms can last a week or so. After about 8-10 days, some people suddenly get worse. They have breathlessness and pneumonia (lung infection) and chest pain. At this point, the patient has to be given immediate and critical care. For about 80% of people, they get well on their own after a week or so. Some people are so mildly ill that they may not even realise they have fallen sick. It is obvious that if a person infects more people, then the total number of persons becoming sick becomes really large. Since there is no cure for this disease, the only way to reduce the spread is to practice physical distancing and wearing a mask. See how you can do this in the accompanying article. In short, SARS-Cov-2 can be contained, just like SARS-Cov was, but it can only be done by community effort. So each one of us has to do our bit. The number of infections across the world has already exceeded a million and thousands have died. Let us all follow good hygiene practices and stay safe, and keep our family safe. Sources: Many from the internet, especially Wikipedia