Viruses Multiply

It’s amazing how something as tiny as viruses can throw a person so off course. Although viruses are invisible to the human eye – and even to some microscopes – their impact can be enormous. Depending on the type of virus, they can cause temporary infections, permanent nesting, exaggerated immune responses, warts or even tumor formation. So it pays to know.

Content

  • Virus definition
  • The structure of viruses
  • Other common types of viruses
  • Infectious diseases caused by viruses

Virus definition

In simple terms, viruses are infectious agents that require a living body cell to replicate and are classified as parasites [1]. Possible cells serving as “hosts” can originate either from humans, animals, plants or even bacteria. However, not every type of virus is capable of infecting any of these organisms [1]. Viruses can also exist outside of a host cell. They are then referred to as “virions” or “extracellular virus particles”. Only then, viruses cannot reproduce in this way [1].

What exactly is a virus?

Viruses – like somatic cells – have their own genome. However, depending on the virus, it can be either a DNA (“double-stranded”) or an RNA (“single-stranded copy”) [1]. The reason why viruses are dependent on host cells is that they lack important components that are indispensable for reproduction. They do not have their own “machinery” for protein synthesis. However, the production of proteins is essential for the replication and thus the long-term survival of a virus strain [1].

The life cycle of a virus can be thought of as follows.

First, viruses must be transmitted from one organism to the next. This can occur, for example, from human to human, animal to animal, or even sometimes animal to human [2]. The exact route of transmission, on the other hand, varies from virus to virus. In principle, transmission is possible via saliva exchange, via stool particles that enter the mouth, via the blood, via semen, via vaginal secretions, as droplet infection via the respiratory air, and via certain “vectors” (e.g., certain tropical mosquito species) [3].

The life of a virus

Once viruses have entered an appropriate organ (e.g., the respiratory tract in the case of coronavirus), they undergo a specific sequence of steps in the cells there [2]. The first of these steps is the so-called “adsorption”, i.e. attachment to the host cell. This is because infection can only occur if the virus matches certain surface characteristics of the cell [2]. This is followed by the so-called “penetration”, i.e. the penetration into the interior of the cell. This can take place quite differently depending on the type of virus. Often, the virus is “swallowed” by the cell, so to speak, or is specifically transported inside. In other cases, the virus and cell simply merge. The comparison with a Trojan horse is always apt here [2]. If penetration is successful, the next step is uncoating. The viral genome is released. In a sense, the inside of the Trojan horse can now reach the outside and “enter the fortress” [2]. With the help of the protein synthesis apparatus of the host cell, the so-called “replication” can take place next. The viral genome is replicated. New viral proteins are formed. In a so-called “assembly” phase, all virus components are then also assembled [2]. Thus, as the last step, the newly formed virus can leave the host cell again and infect further cells [2].

The assembly of viruses

In addition to the differences in the viral genome (DNA or RNA), other components of viruses can also be different. For example, a distinction is made between enveloped and naked viruses, since not every virus has an outer viral envelope [4]. Different types of viruses at a glance What all viruses have in common, however, is the so-called capsid. This is a protein envelope surrounding the viral genome. However, as can be seen from the figure above, the exact configuration of the viral capsid varies [4].

Viruses and bacteria – what is the difference?

Viruses and bacteria can sometimes cause very similar disease patterns. However, there are clear differences in structure and composition between the two groups of pathogens [5]. This is particularly important to know because it results in completely different treatment options [5]. Unlike viruses, bacteria are small, unicellular organisms. Therefore, under suitable environmental conditions, bacteria can multiply outside of another organism – in contrast to viruses [5]. In contrast to humans, animals or plants, bacteria do not have a cell nucleus [5]. Also, by far not all bacteria cause illness. On the contrary. Many bacterial strains are essential for humans and are important components of a healthy intestinal or skin flora [5].

Mutation of viruses

Viruses can change their genetic material through so-called mutations. Namely, if errors occur during the “replication phase” described above, these small genetic changes can occur [2]. In the vast majority of cases, this would compromise the virus’ ability to function. Nevertheless, mutations are helpful for the long-term persistence of the “virus offspring”. This is because new variations of the virus can be created that may be able to withstand more difficult conditions [2]. A good example in this regard is the coronavirus. For example, the omicron mutation of the SARS-CoV-2 virus alone has 32 mutations at the so-called “spike protein,” 10 of which are in the area that docks to the body’s cells and thus allows them to enter the cell. All in all, this makes it easier for omicron to escape the immune system via “immune escape” and to reinfect even vaccinated or recovered individuals [6, 7]. Now and then, it is also possible for an organism to be infected by two different viral strains at the same time. For example, in the case of the influenza virus. In this case, entire gene segments can be exchanged, resulting in a completely new subtype. This is known as an “antigenic shift” [2].

Omicron variant of the coronavirus

The SARS-CoV-2 coronavirus is an RNA virus that has a viral envelope (see above). It has the closest genetic similarity to two other coronaviruses, but these are found only among bats [8]. This makes bats at least likely as the original source of SARS-CoV-2. However, there may well have been another intermediate host [8]. The surface feature of cells to which SARS-CoV-2 can attach (“adsorption” phase) is the so-called angiotensin-converting enzyme 2 (ACE2). In this case, the attachment occurs via the so-called “spike protein” of the coronavirus [8]. The more than 30 mutations in the spike protein that occurred in Omikron are the main reason for the increased transmissibility and the overall reduced sensitivity to neutralizing antibodies [8]. Compared to the delta variant, Omikron also appears to replicate much more rapidly. In contrast, the risk of becoming severely ill with corona infection has decreased on average with omicron. However, this is still possible – especially for risk groups and unvaccinated individuals [8].

Other common virus types

It is true that viruses have many similarities in structure. Nevertheless, there are numerous differences. This is expressed in particular in the way in which they are ultimately transmitted, which organ system they affect and which signs of illness they can cause as a result. The following overview provides a summary of some of the globally most important virus types. These include the Epstein-Barr virus, the Ebola virus, the human papillomaviruses, the Zika virus, the norovirus, the hantavirus, the hepatitis viruses, the HI virus (find information on the novelties in HIV vaccination here), influenza viruses and, last but not least, herpes simplex viruses [9-17]: Transmission routes, distribution and signs of illness of important viruses Since many of these viral diseases can consequently be accompanied by quite serious consequences of illness, the question of possible treatment options naturally arises. And here, too, there are important things to bear in mind.

Infectious diseases caused by viruses

The basic distinction here is between treatments that are intended to alleviate the symptoms triggered by viruses and those that target the virus itself – i.e. combat the actual cause.

Symptoms and treatment

For most viruses, the only option currently available is to treat severe symptoms “symptomatically”. This applies, for example, to most cold viruses, in which the symptoms appear rapidly but fortunately also subside quickly [18]. In this case, it is still possible to reduce fever with drugs such as paracetamol. However, it is not yet possible to stop the viruses [18]. In certain cases, however, there are drugs that can be used to specifically “fight” the virus. These are the so-called “virustatics”. It is important to note that these drugs primarily have a preventive effect. In other words, they can prevent the virus from multiplying in the body. However, if this has already occurred, the viral disease can take its full course [19]. The various preparations target different steps in the viral life cycle described above. Some stop the virus from attaching and entering the host cell. Others the release and readout of the viral genome. Some interfere with the assembly of viral components. And still others prevent the shedding and release of new viruses from the host cell [19]. Of course, the decision as to whether a suitable preparation is available and whether treatment with it makes sense can only be made together with physicians. The contents of this article reflect the current scientific status at the time of publication and were written to the best of our knowledge and belief. Nevertheless, the article cannot replace medical advice and diagnosis. If you have any questions, consult your general practitioner.   © BZgA Viruses have a relatively simple structure. They consist of one or more molecules and are sometimes surrounded by a protein envelope. The molecules contain the genetic material – i.e. DNA or RNA – with the information for their reproduction. Unlike bacteria, viruses do not consist of their own cell, nor do they have their own metabolism. They have no energy production of their own and no means of protein synthesis. Therefore, strictly speaking, they are not living organisms. Viruses are tiny, only about 20 to 300 nanometers in size. This is why they cannot be seen under an ordinary light microscope, but require an electron microscope. Viruses come in many different forms. Some viruses look almost like tadpoles with a long tail, others are round or even rod-shaped. Not all viruses in our environment infect humans. And not all viruses that infect humans actually make us sick. This is because our immune system often reacts quickly and successfully fights off the invaders. Nevertheless, there are important diseases that are triggered by viruses. Viruses invade animal, plant or human cells. They use these living cells as “host cells.” They can also persist in the environment, sometimes for a very long time, and remain contagious. However, if they do not find a new host cell, they die sooner or later. To reproduce, viruses also need host cells. As soon as the pathogens enter our body – i.e. we have become infected – the viruses begin to multiply. The virus attaches itself to the host cell and lets it produce the building blocks it needs. Once the genetic material of the virus is released, the host cell is forced to produce numerous virus particles and assemble them into new viruses. The host cell then dies and thousands of viruses are released, which immediately set out to find a new host cell. Host cells can be, for example, red and white blood cells, but also liver cells, muscle cells and others. As long as we are ill, we excrete the pathogens, often for some time afterwards. It is not easy to fight viruses with drugs. Antibiotics, for example, are ineffective against viral diseases. There are so-called antiviral drugs, but these only help against individual types of virus. However, once our body’s own defenses have dealt with the pathogen, we are in many cases immune to that virus. We are then unable to contract the same pathogen a second time. Viruses are flexible: the flu virus (influenza virus), for example, is constantly changing its face, making it easier to get past the body’s own defenses. That’s why the flu vaccine only protects for one year, because by the next wave of influenza, the quick-change artist may have already changed its appearance again. The vaccine is adapted annually to the characteristics of the flu viruses that are currently on the way or are expected. Viruses can cause harmless illnesses such as a common cold or even cold sores. Most of the gastrointestinal infections in this country are also caused by viruses. But serious infections such as HIV/AIDS or inflammation of the liver (hepatitis) are also caused by viruses. Viruses also cause many of the so-called classic childhood diseases such as chickenpox, measles or rubella.

Viruses: Where they come from, how they multiply and what works against them

Viruses seek out foreign host cells, such as red blood cells, to multiply. © Source: imago Viruses can make people ill – this has been known not only since the worldwide spread of the new coronavirus Sars-CoV-2. We clarify what viruses trigger in the human body in their search for a host cell, which drugs work against them and which virus species there are. Michèle Förster Daily news coverage currently revolves around the novel Sars-CoV-2 coronavirus around the world. In parallel with the spread of lung disease, plenty of fears, speculations and rumors are also emerging. How do viruses spread, what treatment helps and what vaccinations protect against them? An overview is provided by the Federal Center for Health Education (BZgA). Read more after the ad Read more after the ad Viruses are tiny, only about 20 to 300 nanometers in size and very simple in structure. They consist of one molecule and are usually surrounded by a protein envelope called a capsid. Viruses contain a hereditary substance on which the information for reproduction is stored. Unlike bacteria, they have no metabolism of their own and no possibility of protein synthesis. Therefore, unlike bacteria, they do not count as living organisms.

Where do viruses occur?

Viruses need a host cell to survive, which is why they infect humans or animals. However, pathogens also remain contagious for some time in the environment, such as on surfaces. Read more after the ad Read more after the ad

How do viruses reproduce?

Viruses cannot reproduce on their own and always need another living being to survive. Therefore, they infect foreign host cells into which they introduce their own genetic material. Thus, as soon as they have entered the human body and docked onto the host cell, a process of reprogramming begins. The host cell produces more viruses, which immediately start looking for new host cells, and then dies. During this multiplication process, cells in the human body can be destroyed – or the body’s own defenses eliminate the infected cells.

How do viruses survive?

To avoid being destroyed by vaccines, viruses constantly change their external appearance. For this reason, for example, a new vaccine serum is developed every year that is adapted to the changed flu pathogens. Read more after the advertisement Read more after the advertisement

What are the viral diseases?

Viruses differ in the form in which their genetic material is present. A distinction is made between DNA and RNA viruses. The former include, for example, herpes viruses, parvoviruses or papilloma viruses. Effective vaccines are available for some of the DNA viruses. RNA viruses, on the other hand, usually protect their genetic material with an additional envelope. Since changes in the genetic material occur more frequently with this type of virus, it is more difficult to develop a vaccine. This group includes HIV, rubella, hepatitis E, Ebola and the coronaviruses. Not all viruses that infect the human body also make people sick. Often the immune system reacts quickly and manages to successfully fight the pathogens itself.

What works against them?

Viruses cannot be fought with antibiotics. However, there are so-called antiviral drugs that can prevent the reproduction of individual types of viruses. These include, for example, drugs against herpes viruses, influenza or HIV. Some antivirals prevent the virus from docking or entering the host cell, others interfere with the production of the genetic material or the protein coat. Once the body’s own defenses have defeated the pathogen, one is immune to the virus. It is then not possible to contract the same pathogen a second time. Read more after the ad Read more after the ad For the first time in 3D and atomic resolution: researchers from the Department of Molecular Biology at the Max Planck Institute for Biophysical Chemistry, in a collaboration with colleagues in Würzburg, have succeeded in understanding the propagation strategy of vaccinia-viruses. These also serve as vaccines against human smallpox diseases and as the basis for new cancer therapies. (Cell, Dec. 12, 2019) In order for viruses to reproduce, they mostly need the support of the cells they infect. Only in the nucleus of their host cells do they find the machinery, proteins and building blocks with which they can multiply their genetic material before infecting further cells. But not all viruses find their way into the cell nucleus. Some remain outside in the cytoplasm and have to duplicate their genetic material on their own. The necessary “machinery” is provided by the viruses themselves. A special nanomachine, combined with various subunits, plays a key role in this process: RNA polymerase. This cellular copying machine reads the genetic information from the virus’ genome and translates it into messenger RNA – a long molecule that serves as a blueprint for the proteins encoded in the genome. This process is called transcription. Scientists led by Patrick Cramer, Director and Head of the Department of Molecular Biology at the Max Planck Institute (MPI) for Biophysical Chemistry, and Utz Fischer of the Julius Maximilian University (JMU) Würzburg have now succeeded for the first time in visualizing the structure of these nanomachines from poxviruses in three dimensions and at atomic resolution. Henning Urlaub, research group leader at the MPI for Biophysical Chemistry, was also involved in the analyses. The scientists worked with Vacciniaa DNA virus. This pathogen, which is completely harmless to humans, is not only the basis of all vaccines against smallpox. It is also being tested in oncolytic virotherapy to combat cancer.

A molecular clamp that holds everything together

“The vaccinia virus RNA polymerase essentially exists in two manifestations: the actual core enzyme and an even larger complex that has additional, specialized functionalities thanks to added subunits,” Fischer explains. The core enzyme resembles the molecular copying machine that occurs naturally in living cells and is being intensively researched by the Cramer department: RNA polymerase II. The second complex of the Vaccinia-RNA polymerase is an all-rounder. It consists of numerous subunits and carries out the entire transcription process for the virus. This enables the pathogen to replicate. The complex is held together by a molecule that the virus pilfers from its host cell: a so-called transfer RNA (tRNA). This type of molecule normally plays no role in transcription, but provides the amino acid building blocks for protein production. If the host tRNA were not involved, the huge complex would probably fall apart. Molecular structures of vaccinia isolated from infected cells. Vaccinia-transcription complexes. A) Cartoon representation of the Vaccinia-RNA polymerase (RNAP) core enzyme. The individual subunits are highlighted in color. B) Surface representation of the complete Vaccinia RNA polymerase complex. In addition to the core enzyme, this contains viral transcription factors required for the various steps of the transcription cycle, as well as a cellular tRNA (cartoon representation). “> To get to the bottom of how viral RNA polymerase works, the researchers determined its three-dimensional structure during different steps of the transcription process. “With the new findings, we can now trace the entire process of viral replication. Like in a movie, it is possible to follow how this nanomachine functions at the atomic level and how the individual processes are choreographed,” says Cramer. His collaborator, structural biologist Hauke Hillen, adds, “It’s particularly amazing how the building blocks of the machine rearrange themselves after the start of transcription to drive the synthesis of the RNA product – this complex is really very dynamic.” Molecular structure of the Vaccinia-RNA polymerase during transcription. The complete vaccinia RNA polymerase (RNAP) complex (left) undergoes a major conformational rearrangement during interaction with DNA and formation of the actively transcribing capping complex (right).”>

A super microscope provides images of the copying machine

The relevant data are provided by a device that has revolutionized structural analysis in recent years – the cryo-electron microscope. It enables images with a resolution that is on the order of atoms. For their images, the researchers snap-froze and “photographed” RNA polymerase at different stages of transcription. In this way, millions of snapshots were taken of the nanomachine as it worked, which the researchers then assembled into an overall picture. Hillen and his Würzburg colleague Clemens Grimm had to tinker with computers for about six months until they had developed spatial models of the polymerase complexes from several terabytes of data. Using 3D glasses, anyone can now view the complex, rotate it as desired and dissect it into its subunits. Among other things, the new findings offer the possibility of influencing the viral replication cycle, which has therapeutic potential. Studies are currently underway worldwide to investigate Vaccinia-viruses in the fight against cancer. The fact that specially optimized vaccinia-viruses can even shrink tumors and detect the smallest metastases has already been demonstrated by the company Genelux has already demonstrated in animal experiments and on patients. Modified press release of the University of Würzburg/is Viruses Multiply.




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