User:Graham Beards/viruses/Infections in humans

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Roles in human diseases

A photograph of the upper body of a man labelled with the names of viruses that infect the different parts
Overview of the main types of viral infection and the most notable species involved[1][2]

Examples of common human diseases caused by viruses include the

chronic fatigue syndrome.[3] Viruses have different mechanisms by which they produce disease in an organism, which depends largely on the viral species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In multicellular organisms, if enough cells die, the whole organism will start to suffer the effects. Although viruses cause disruption of healthy homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the herpes simplex virus, which causes cold sores, to remain in a dormant state within the human body. This is called latency[4] and is a characteristic of the herpes viruses including Epstein-Barr virus, which causes glandular fever, and varicella zoster virus, which causes chickenpox and shingles. Most people have been infected with at least one of these types of herpes virus.[5] However, these latent viruses might sometimes be beneficial, as the presence of the virus can increase immunity against bacterial pathogens, such as Yersinia pestis.[6]
Some viruses can cause lifelong or
chronic infections, where the viruses continue to replicate in the body despite the host's defence mechanisms.[7] This is common in hepatitis B virus and hepatitis C virus infections. People chronically infected are known as carriers, as they serve as reservoirs of infectious virus.[8] In populations with a high proportion of carriers, the disease is said to be endemic.[9]

Viruses are an established cause of

Merkel cell carcinoma.[12]
Hepatitis viruses can develop into a chronic viral infection that leads to
Hodgkin’s lymphoma, B lymphoproliferative disorder, and nasopharyngeal carcinoma.[17] Merkel cell polyomavirus, which is closely related to the simian SV40 virus, and mouse polyomaviruses have been used as animal models for cancer viruses for over 50 years.[18]

Diagnosis

Koplik spots
a sign of the onset of measles. These appear on the mucosa of the cheeks and tongue, and are irregularly-shaped, bright red spots often with a bluish-white central dot.

For many virus infections, diagnosis can be made from the signs and symptoms alone. Some infections are more difficult to diagnose and laboratory tests are required. In humans and other animals, blood tests are often used because when the

immunity are carried out.[20] Other tests include those that allow the detection of the virus's DNA (or RNA) in samples of blood and other bodily fluids, and those that can react with parts of the viruses called antigens that can be found in infected fluids and cells.[21]

Epidemiology

1918 influenza
virus

Viral epidemiology is the branch of medical science that deals with the transmission and control of virus infections in humans. Transmission of viruses can be vertical, that is from mother to child, or horizontal, which means from person to person. Examples of vertical transmission include hepatitis B virus and HIV where the baby is born already infected with the virus.[22] Another, rarer, example is the varicella zoster virus, which, although causing relatively mild infections in humans, can be fatal to the foetus and new-born baby.[23]

dengue
. The rate or speed of transmission of viral infections depends on factors that include population density, the number of susceptible individuals, (i.e., those not immune),[24] the quality of healthcare and the weather.[25]

Epidemiology is used to break the chain of infection in populations during outbreaks of viral diseases.[26] Control measures are used that are based on knowledge of how the virus is transmitted. It is important to find the source, or sources, of the outbreak and to identify the virus. Once the virus has been identified, the chain of transmission can sometimes be broken by vaccines. When vaccines are not available sanitation and disinfection can be effective. Often infected people are isolated from the rest of the community and those that have been exposed to the virus placed in quarantine.[27] To control the outbreak of foot-and-mouth disease in cattle in Britain in 2001, thousands of cattle were slaughtered.[28] Most viral infections of humans and other animals have incubation periods during which the infection causes no signs or symptoms.[29] Incubation periods for viral diseases range from a few days to weeks but are known for most infections.[30] Somewhat overlapping, but mainly following the incubation period, there is a period of communicability; a time when an infected individual or animal is contagious and can infect another person or animal.[30] This too is known for many viral infections and knowledge the length of both periods is important in the control of outbreaks.[31] When outbreaks cause an unusually high proportion of cases in a population, community or region they are called epidemics. If outbreaks spread worldwide they are called pandemics.[32]

Host defence mechanisms

The body's first line of defence against viruses is the innate immune system. This comprises cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognise, and respond to, pathogens in a generic way, but, unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host.[33]

RNA interference is an important innate defence against viruses.[34] Many viruses have a replication strategy that involves double-stranded RNA (dsRNA). When such a virus infects a cell, it releases its RNA molecule or molecules, which immediately bind to a protein complex called dicer that cuts the RNA into smaller pieces. A biochemical pathway called the RISC complex is activated, which degrades the viral mRNA and the cell survives the infection. Rotaviruses avoid this mechanism by not uncoating fully inside the cell and by releasing newly produced mRNA through pores in the particle's inner capsid. The genomic dsRNA remains protected inside the core of the virion.[35][36]

When the

immunity are carried out.[38]

Two spherical rotavirus particles, one is coated with antibody which looks like many small birds, regularly spaced on the surface of the virus
Two rotaviruses: the one on the right is coated with antibodies that stop its attaching to cells and infecting them

A second defence of vertebrates against viruses is called cell-mediated immunity and involves immune cells known as T cells. The body's cells constantly display short fragments of their proteins on the cell's surface, and, if a T cell recognises a suspicious viral fragment there, the host cell is destroyed by killer T cells and the virus-specific T-cells proliferate. Cells such as the macrophage are specialists at this antigen presentation.[39] The production of interferon is an important host defence mechanism. This is a hormone produced by the body when viruses are present. Its role in immunity is complex; it eventually stops the viruses from reproducing by killing the infected cell and its close neighbours.[40]

Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing the amino acid sequence of the proteins on the surface of the virion. These persistent viruses evade immune control by sequestration, blockade of antigen presentation, cytokine resistance, evasion of natural killer cell activities, escape from apoptosis, and antigenic shift.[41] Other viruses, called neurotropic viruses, are disseminated by neural spread where the immune system may be unable to reach them.

Many virus infections are spread from person to person and immunity in a proportion of the population can protect susceptible individuals because the chain of transmission is broken. This is known as herd immunity. The reproductive rate – the number of further cases caused by an infected person — is known for many virus infections. If this rate is reduced to less than one, the infection will stop spreading. And if humans are the only host for the virus, the disease can be eradicated.[42]

Estimated Herd Immunity thresholds for some vaccine preventable viral infections[43]
Disease Transmission R0 Herd immunity threshold
Measles Airborne 12–18 83–94%
Mumps Airborne droplet 4–7 75–86%
Polio Fecal-oral route 5–7 80–86%
Rubella Airborne droplet 5–7 80–85%
Smallpox Social contact 6–7 83–85%
^ - R0 is the basic reproduction number, or the average number of secondary infectious cases that are produced by a single index case in completely susceptible population.

Prevention and treatment

Because viruses use vital metabolic pathways within host cells to replicate, they are difficult to eliminate without using drugs that cause toxic effects to host cells in general. The most effective medical approaches to viral diseases are

antiviral drugs that selectively interfere with viral replication.[44][45]

Vaccines

Vaccination is a cheap and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity (illness) and mortality (death) associated with viral infections such as

antigens).[50]
Live vaccines contain weakened forms of the virus, which do not cause the disease but, nonetheless, confer immunity. Such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity, (who are described as
immunocompromised patients because they cannot cause the disease.[53]
The yellow fever virus vaccine, a live-attenuated strain called 17D, is probably the safest and most effective vaccine ever generated.[54]

The structure of DNA showing the position of the nucleosides and the phosphorus atoms that form the "backbone" of the molecule

Antiviral drugs

Guanosine
The guanosine analogue Aciclovir

Antiviral drugs are often

hydroxyl groups, which, along with phosphorus atoms, link together to form the strong "backbone" of the DNA molecule. This is called DNA chain termination.[55] Examples of nucleoside analogues are aciclovir for Herpes simplex virus infections and lamivudine for HIV and Hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs.[56]
Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the
protease inhibitors that inactivate this enzyme.[57]

Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease is chronic, and without treatment, they are infected for the remainder of their lives. However, there is now an effective treatment that uses the nucleoside analogue drug ribavirin combined with interferon.[58] The treatment of chronic carriers of the hepatitis B virus by using a similar strategy using lamivudine has been developed.[59]


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