These mutations can be of particular importance with the development of drug resistant strains of virus. Disease does not always follow successful virus replication in the target organ. Disease occurs only if the virus replicates sufficiently to damage essential cells directly, to cause the release of toxic substances from infected tissues, to damage cellular genes or to damage organ function indirectly as a result of the host immune response to the presence of virus antigens.
As a group, viruses use all conceivable portals of entry, mechanisms of spread, target organs, and sites of excretion. This abundance of possibilities is not surprising considering the astronomic numbers of viruses and their variants see Ch. Direct cell damage and death may result from disruption of cellular macromolecular synthesis by the infecting virus. Also, viruses cannot synthesize their genetic and structural components, and so they rely almost exclusively on the host cell for these functions.
Their parasitic replication therefore robs the host cell of energy and macromolecular components, severely impairing the host's ability to function and often resulting in cell death and disease. Pathogenesis at the cellular level can be viewed as a process that occurs in progressive stages leading to cellular disease. As noted above, an essential aspect of viral pathogenesis at the cellular level is the competition between the synthetic needs of the virus and those of the host cell. Since viruses must use the cell's machinery to synthesize their own nucleic acids and proteins, they have evolved various mechanisms to subvert the cell's normal functions to those required for production of viral macromolecules and eventually viral progeny.
The function of some of the viral genetic elements associated with virulence may be related to providing conditions in which the synthetic needs of the virus compete effectively for a limited supply of cellular macromolecule components and synthetic machinery, such as ribosomes. Damage of cells by replicating virus and damage by the immune response are considered further in Chapters 44 and 50 , respectively.
Most viruses have an affinity for specific tissues; that is, they display tissue specificity or tropism. This specificity is determined by selective susceptibility of cells, physical barriers, local temperature and pH, and host defenses. Many examples of viral tissue tropism are known. Polioviruses selectively infect and destroy certain nerve cells, which have a higher concentration of surface receptors for polioviruses than do virus-resistant cells.
Rhinoviruses multiply exclusively in the upper respiratory tract because they are adapted to multiply best at low temperature and pH and high oxygen tension. Enteroviruses can multiply in the intestine, partly because they resist inactivation by digestive enzymes, bile, and acid.
The cell receptors for some viruses have been identified. Rabies virus uses the acetylcholine receptor present on neurons as a receptor, and hepatitis B virus binds to polymerized albumin receptors found on liver cells. Similarly, Epstein-Barr virus uses complement CD21 receptors on B lymphocytes, and human immunodeficiency virus uses the CD4 molecules present on T lymphocytes as specific receptors. Viral tropism is also dictated in part by the presence of specific cell transcription factors that require enhancer sequences within the viral genome.
Recently, enhancer sequences have been shown to participate in the pathogenesis of certain viral infections. Enhancer sequences within the long terminal repeat LTR regions of Moloney murine leukemia retrovirus are active in certain host tissues. In addition, JV papovavirus appears to have an enhancer sequence that is active specifically in oligodendroglia cells, and hepatitis B virus enhancer activity is most active in hepatocytes.
Tissue tropism is considered further in Chapter Viruses are carried to the body by all possible routes air, food, bites, and any contaminated object. Similarly, all possible sites of implantation all body surfaces and internal sites reached by mechanical penetration may be used. The frequency of implantation is greatest where virus contacts living cells directly in the respiratory tract, in the alimentary tract, in the genital tract, and subcutaneously.
With some viruses, implantation in the fetus may occur at the time of fertilization through infected germ cells, as well as later in gestation via the placenta, or at birth. Even at the earliest stage of pathogenesis implantation , certain variables may influence the final outcome of the infection. For example, the dose, infectivity, and virulence of virus implanted and the location of implantation may determine whether the infection will be inapparent subclinical or will cause mild, severe, or lethal disease.
Successful implantation may be followed by local replication and local spread of virus Fig. Virus that replicates within the initially infected cell may spread to adjacent cells extracellularly or intracellularly. Extracellular spread occurs by release of virus into the extracellular fluid and subsequent infection of the adjacent cell. Intracellular spread occurs by fusion of infected cells with adjacent, uninfected cells or by way of cytoplasmic bridges between cells.
Most viruses spread extracellularly, but herpesviruses, paramyxoviruses, and poxviruses may spread through both intracellular and extra cellular routes. Intracellular spread provides virus with a partially protected environment because the antibody defense does not penetrate cell membranes.
Virus spread during localized infection. Numbers indicate sequence of events. Spread to cells beyond adjacent cells may occur through the liquid spaces within the local site e. Also, infected migratory cells such as lymphocytes and macrophages may spread the virus within local tissue. Establishment of infection at the portal of entry may be followed by continued local virus multiplication, leading to localized virus shedding and localized disease.
In this way, local sites of implantation also are target organs and sites of shedding in many infections Table Respiratory tract infections that fall into this category include influenza, the common cold, and parainfluenza virus infections. Alimentary tract infections caused by several gastroenteritis viruses e. Localized skin infections of this type include warts, cowpox, and molluscum contagiosum.
Localized infections may spread over body surfaces to infect distant surfaces. An example of this is the picornavirus epidemic conjunctivitis shown in Figure ; in the absence of viremia, virus spreads directly from the eye site of implantation to the pharynx and intestine. Other viruses may spread internally to distant target organs and sites of excretion disseminated infection.
A third category of viruses may cause both local and disseminated disease, as in herpes simplex and measles. Spread of picornavirus over body surfaces from eye to pharynx and intestine during natural infection.
Local neutralizing antibody activity is shown. At the portal of entry, multiplying virus contacts pathways to the blood and peripheral nerves, the principal routes of widespread dissemination through the body. The most common route of systemic spread of virus involves the circulation Fig.
Viruses such as those causing poliomyelitis, smallpox, and measles disseminate through the blood after an initial period of replication at the portal of entry the alimentary and respiratory tracts , where the infection often causes no significant symptoms or signs of illness because the virus kills cells that are expendable and easily replaced. Virus progeny diffuse through the afferent lymphatics to the lymphoid tissue and then through the efferent lymphatics to infect cells in close contact with the bloodstream e.
This initial spread may result in a brief primary viremia. Subsequent release of virus directly into the bloodstream induces a secondary viremia, which usually lasts several days and puts the virus in contact with the capillary system of all body tissues.
Virus may enter the target organ from the capillaries by replicating within a capillary endothelial cell or fixed macrophage and then being released on the target organ side of the capillary. Virus may also diffuse through small gaps in the capillary endothelium or penetrate the capillary wall through an infected, migrating leukocyte. The virus may then replicate and spread within the target organ or site of excretion by the same mechanisms as for local dissemination at the portal of entry.
Disease occurs if the virus replicates in a sufficient number of essential cells and destroys them. For example, in poliomyelitis the central nervous system is the target organ, whereas the alimentary tract is both the portal of entry and the site of shedding. In some situations, the target organ and site of shedding may be the same. Virus spread through bloodstream during a generalized infection. Dissemination through the nerves is less common than bloodstream dissemination, but is the means of spread in a number of important diseases Fig.
This mechanism occurs in rabies virus, herpesvirus, and, occasionally, poliomyelitis virus infections. For example, rabies virus implanted by a bite from a rabid animal replicates subcutaneously and within muscular tissue to reach nerve endings. Evidence indicates that the virus spreads centrally in the neurites axons and dendrites and perineural cells, where virus is shielded from antibody. This nerve route leads rabies virus to the central nervous system, where disease originates.
Rabies virus then spreads centrifugally through the nerves to reach the salivary glands, the site of shedding. Table shows other examples of nerve spread. Virus spread through nerves during a generalized infection. COVID is spread in three main ways: Breathing in air when close to an infected person who is exhaling small droplets and particles that contain the virus. Having these small droplets and particles that contain virus land on the eyes, nose, or mouth, especially through splashes and sprays like a cough or sneeze.
Touching eyes, nose, or mouth with hands that have the virus on them. These changes happen over time and can lead to the emergence of variants that may have new characteristics. Vaccines are highly effective against severe illness. Find a vaccine. Wear a mask that covers your nose and mouth to help protect yourself and others. Avoid crowds and poorly ventilated indoor spaces.
Test to prevent spread to others. Wash your hands often with soap and water. What You Need to Know If you are not fully vaccinated and aged 2 or older, you should wear a mask in indoor public places. In general, you do not need to wear a mask in outdoor settings. In areas with high numbers of COVID cases , consider wearing a mask in crowded outdoor settings and for activities with close contact with others who are not fully vaccinated.
Facebook Twitter LinkedIn Syndicate. Your body has a number of defensive barriers to prevent infection. Hair-like structures called cilia line our airways and constantly move in a beating motion to expel the mucus and replace it with a new layer of mucus. Basically, your body works hard to get rid of viruses.
All of these defenses provide the first line of the host immune response against a range of airborne pathogens. This means that the more virions that get in, the more likely infection is to occur. In addition, we should note that in order to be infectious, virions must be intact. When a virion sits out in the world — say, on a milk carton or cereal box at the store — it degrades. Once it is no longer intact, it retains some of the genetic material of the virus, but is too damaged to be infectious.
When scientists test for the virus on surfaces and in the environment, they are actually testing for the genetic material. Instead, it needs to hijack the machinery of your cells to replicate.
To do this, it needs to get hold of cells and unlock them. Viruses can do this with the different "keys" it has on its surface. Different viruses have individualized keys that can unlock different cells in the human body. This ACE2 receptor is present throughout our airway and lungs, and possibly in the gastrointestinal tract.
It is also present in our blood vessels. The main target cells seem to be the cells that line our lungs. Once the virus locks onto a cell, it uses the cell's own machinery to fuse and enter the cell. And then it gets to work. This has so far proven to be an effective method for vaccine development.
It uses parts of the cell to package these proteins. The packages gather at the edge of the cell and then bud off to form new virus particles. As these new virus particles exit the cell, the human cell it infected dies. Your cells essentially burst and all of the contents leak out, including components that are damaging to other cells.
This may sound scary, but it is important to remember that our body is used to this. And you have tools to deal with it. Your immune system gears up to fight. In fact, there are two separate immune responses: the innate immune response and the adaptive immune response. When it does recognize the virus, it deploys first the innate immune system which consists of barrier defenses such as the mucus and cilia and also tight junctions between cells , secreted chemicals, and white blood cells.
There are several different types of key white blood cells — macrophages, dendritic cells, and neutrophils — and they all have slightly different methods of attack. In general, though, these white blood cells are able to broadly recognize and attack a wide variety of organisms that can cause disease, whether they be bacteria, fungi, or viruses like SARS-CoV In some cases white blood cells can identify your own cells that have been infected and induce them to kill themselves before the replicated virus can get out.
The innate immune response causes many symptoms of illness. This response is targeted rather than general — that is, it is a response that is specific to this virus. The adaptive immune response involves, for instance, the production of antibodies to the virus. They all have slightly different functions, but in the end they work together to kill the virus. The innate and adaptive immune responses are the same ones that your body deploys to fight all kinds of viruses the flu, measles, etc.
This is especially true if the virus is contained to the upper respiratory tract causing symptoms such as sore throat, cough, fever, etc.
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