In addition, disease may result from a late immune reaction to viral antigen e. Virus replication in the target organ resembles replication at other body sites except that 1 the target organ in systemic infections is usually reached late during the stepwise progression of virus through the body, and 2 clinical disease originates there.
At each step of virus progression through the body, the local recovery mechanisms local body defenses, including interferon, local inflammation, and local immunity are activated.
Thus, when the target organ is infected, the previously infected sites may have reached various stages of recovery. Figure illustrates this staging of infection and recovery in different tissues during a spreading surface infection. Circulating interferon and immune responses probably account for the termination of viremia, but these responses may be too late to prevent seeding of virus into the target organ and into sites of shedding. Nevertheless, these systemic defenses can diffuse in various degrees into target organs and thereby help retard virus replication and disease.
Depending on the balance between virus and host defenses see Chs. Additional constitutional disease such as fever and malaise may result from diffusion of toxic products of virus replication and cell necrosis, as well as from release of lymphokines and other inflammatory mediators.
Release of leukotriene C4 during respiratory infection may cause bronchospasm. Viral antigens also may participate in immune reactions, leading to disease manifestations. In addition, impairment of leukocytes and immunosuppression by some viruses may cause secondary bacterial infection. Because of the diversity of viruses, virtually every possible site of shedding is utilized Table ; however, the most frequent sites are the respiratory and alimentary tracts. Blood and lymph are sites of shedding for the arboviruses, since biting insects become infected by this route.
HIV is shed in blood and semen. Milk is a site of shedding for viruses such as some RNA tumor viruses retroviruses and cytomegalovirus a herpesvirus. Several viruses e. The genital tract is a common site of shedding for herpesvirus type 2 and may be the route through which the virus is transmitted to sexual partners or the fetus.
Saliva is the primary source of shedding for rabies virus. Cytomegalovirus is also shed from these last two sites. Finally, viruses such as tumor viruses that are integrated into the DNA of host cells can be shed through germ cells. Infection of the fetus is a special case of infection in a target organ. The factors that determine whether a target organ is infected also apply to the fetus, but the fetus presents additional variables. The immune and interferon systems of the very young fetus are immature.
This immaturity, coupled with the partial placental barrier to transfer of maternal immunity and interferon, deprive the very young fetus of important defense mechanisms. Another variable is the high vulnerability to disruption of the rapidly developing fetal organs, especially during the first trimester of pregnancy.
Furthermore, susceptibility to virus replication may be modulated by the undifferentiated state of the fetal cells and by hormonal changes during pregnancy. Although virus multiplication in the fetus may lead to congenital anomalies or fetal death, the mother may have only a mild or inapparent infection.
To cause congenital anomalies, virus must reach the fetus and multiply in it, thereby causing maldeveloped organs. Generally, virus reaches the fetus during maternal viremia by infecting or passing through the placenta to the fetal circulation and then to fetal target organs.
Sufficient virus multiplication may disrupt development of fetal organs, especially during their rapid development the first trimester of pregnancy. Although many viruses occasionally cause congenital anomalies, cytomegalovirus and rubella virus are the most common offenders.
Virus shedding by the congenitally infected newborn infant may occur as a result of persistence of the virus infection at sites of shedding.
Turn recording back on. National Center for Biotechnology Information , U. Show details Baron S, editor. Search term. General Concepts Pathogenesis Pathogenesis is the process by which an infection leads to disease. Cellular Pathogenesis Direct cell damage and death from viral infection may result from 1 diversion of the cell's energy, 2 shutoff of cell macromolecular synthesis, 3 competition of viral mRNA for cellular ribosomes, 4 competition of viral promoters and transcriptional enhancers for cellular transcriptional factors such as RNA polymerases, and inhibition of the interferon defense mechanisms.
Tissue Tropism Viral affinity for specific body tissues tropism is determined by 1 cell receptors for virus, 2 cell transcription factors that recognize viral promoters and enhancer sequences, 3 ability of the cell to support virus replication, 4 physical barriers, 5 local temperature, pH, and oxygen tension enzymes and non-specific factors in body secretions, and 6 digestive enzymes and bile in the gastrointestinal tract that may inactivate some viruses.
Implantation at the Portal of Entry Virions implant onto living cells mainly via the respiratory, gastrointestinal, skin-penetrating, and genital routes although other routes can be used. Local Replication and Local Spread Most virus types spread among cells extracellularly, but some may also spread intracellularly.
Dissemination from the Portal of Entry Viremic : The most common route of systemic spread from the portal of entry is the circulation, which the virus reaches via the lymphatics. Incubation Period The incubation period is the time between exposure to virus and onset of disease. Multiplication in Target Organs Depending on the balance between virus and host defenses, virus multiplication in the target organ may be sufficient to cause disease and death.
Shedding of Virus Although the respiratory tract, alimentary tract, urogenital tract and blood are the most frequent sites of shedding, diverse viruses may be shed at virtually every site. Introduction Pathogenesis is the process by which virus infection leads to disease. Cellular Pathogenesis Direct cell damage and death may result from disruption of cellular macromolecular synthesis by the infecting virus.
Tissue Tropism Most viruses have an affinity for specific tissues; that is, they display tissue specificity or tropism. Sequence of Virus Spread in the Host Implantation at Portal of Entry Viruses are carried to the body by all possible routes air, food, bites, and any contaminated object. Local Replication and Local Spread Successful implantation may be followed by local replication and local spread of virus Fig.
Figure Virus spread during localized infection. Figure Spread of picornavirus over body surfaces from eye to pharynx and intestine during natural infection. Dissemination from the Portal of Entry Dissemination in the Bloodstream At the portal of entry, multiplying virus contacts pathways to the blood and peripheral nerves, the principal routes of widespread dissemination through the body.
Figure Virus spread through bloodstream during a generalized infection. Dissemination in Nerves Dissemination through the nerves is less common than bloodstream dissemination, but is the means of spread in a number of important diseases Fig. Although it is possible for domestic poultry to become infected with avian influenza from direct contact with wild birds, it is more likely that avian influenza viruses are spread indirectly to poultry on contaminated feed, clothing, and equipment.
Agricultural agencies encourage producers to prevent wild birds and other wildlife from coming into direct contact with their poultry, and to avoid To learn more about the impacts of avian influenza on wild birds and the role wild birds may play in the spread of the virus, experts from government agencies have gathered samples from hundreds of thousands of live-captured, apparently healthy wild birds, hunter-harvested birds, and dead wild birds of all species.
AI viruses are also classified into two groups based on their ability to produce Avian influenza AI is caused by an influenza type A virus that can infect poultry such as chickens, turkeys, pheasants, quail, domestic ducks, geese, and guinea fowl. It is carried by wild waterfowl ducks and geese and shorebirds. Each combination is considered a different subtype and can be further broken down into different strains. Chronic wasting disease CWD is a fatal, neurological illness occurring in North American cervids members of the deer family , including white-tailed deer, mule deer, elk, and moose.
Since its discovery in , CWD has spread geographically and increased in prevalence locally. CWD is contagious; it can be transmitted freely within and among cervid populations. No treatments or vaccines are White-nose syndrome is an emergent disease of hibernating bats that has spread from the northeastern to the central United States at an alarming rate.
Since the winter of , millions of insect-eating bats in at least 37 states and seven Canadian provinces have died from this devastating disease. The disease is named for the white fungus, Pseudogymnoascus destructans, that infects skin of West Nile Virus WNV has been detected in at least 48 species of mosquitoes, over species of birds, at least 2 species of reptiles, and more than 25 mammalian species, including horses and humans. Birds are the natural host and reservoir of WNV. Although other animals are susceptible to WNV infection, only birds develop a high enough virus load to transmit the infection to an uninfected Some avian influenza, or bird flu, viruses that are able to enter North America from other continents through migrating birds can be deadly to poultry Due to the global threat to health and human safety posed by avian influenza monitoring has been conducted in the United States to determine the Ducks in North America can be carriers of avian influenza viruses similar to those found in a outbreak in Indiana that led to the losses of Geological Survey released additional evidence that western Alaska remains a hot spot for avian influenza to enter North The avian flu virus that caused widespread harbor seal deaths in can easily spread to and infect other mammals and potentially humans.
The North Atlantic region is a newly discovered important pathway for avian influenza to move between Europe and North America, according to a U. Without such blanket genome sequencing in every part of the world, the threat of an epidemic morphing into a pandemic increases dramatically because no one is safe until everyone is safe. Yet even in the United States, we have an assortment of states and local entities doing different types of sequencing with different levels of comprehensiveness.
For this reason, the U. Early in , I proposed an international Bio Force to track the growing variety of Covid mutations and monitor future threats in the form of pandemics, bioterrorism or antimicrobial resistance.
We need a public-private partnership to engage in automated bio surveillance and then store, analyze and share the data received. Private entities can reveal a surge of illness in a particular area through various input signals. For example, health care data on body temperatures in a defined area can be compiled by local public health agencies while genetic sequencing of wastewater can detect and identify unexpected pathogens in communities — and do so in real time.
A public-private global group could harness data sources like these to offer a state-of-the art global biothreats detection service on a hyperlocal level via subscription to governments or other entities, with all of its sources having the advantage of being anonymized, allaying concerns about privacy.
Of course, winning against future biological threats also means supporting the creation of new vaccines and related drug discoveries. Asian H5N1 was first detected in humans in during a poultry outbreak in Hong Kong and has since been detected in poultry and wild birds in more than 50 countries in Africa, Asia, Europe, and the Middle East. Since its widespread re-emergence in , rare, sporadic human infections with this virus have been reported in Asia, and later in Africa, Europe, and the Middle East.
Human infections with Asian H5N1 viruses have been associated with severe disease and death. Most human infections with avian influenza viruses, including HPAI Asian H5N1 viruses, have occurred after prolonged and close contact with infected birds.
Rare human-to-human spread with this virus has occurred, but it has not been sustained and no community spread of this virus has ever been identified. The H5N1 virus recently detected in U. Flu viruses are constantly changing and animal flu viruses can change such that they may gain the ability to infect people easily and spread among people, causing a pandemic.
Human infections with novel avian influenza virus like Asian H5N1 are concerning because of this pandemic potential.
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