More on Viruses

Role of Viruses in Human Diseases

Examples of common human diseases caused by viruses include the common cold, influenza, chickenpox to mention some. Many serious diseases such as, AIDS, avian influenza, and SARS are caused by viruses. The ability of viruses to cause disease is called virulence.

Other diseases are under investigation to discover if they have a virus as the causative agent, such as the possible connection between human herpesvirus6, (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome. 

Viruses have different mechanisms by which they produce disease in an organism, and 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 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. These latent viruses might sometimes be beneficial, as the presence of the virus can increase immunity against bacterial pathogens, such as Yersinia Pestis.

Some viruses can cause lifelong or chronic infections, where the viruses continue to replicate in the body despite the host’s defense mechanisms. 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. In populations with a high proportion of carriers, the disease is said to be endemic.

Host Defense Mechanisms

The body’s first line of defense against viruses is the innate immune system which is made by cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognize and respond to pathogens in a generic way, but it does not confer long-lasting or protective immunity to the host so as the adaptive immune system does.

RNA interference is an important innate defense against viruses, many viruses have a replication strategy that involves double-stranded RNA (dsRNA). When a virus like this infects a cell, it releases its RNA molecule or molecules which immediately bind to a protein complex that cuts the RNA into smaller pieces. A biochemical pathway ensures cell survival by degrading the viral mRNA. Rotaviruses have evolved to avoid this defense mechanism by skipping the uncoating and releasing newly produced mRNA through pores in the particle’s inner capsid. Their genomic dsRNA remains protected inside the core of the virion

When the adaptive immune system of a vertebrate encounters a virus, it produces specific antibodies that bind to the virus and often render it non-infectious. This is called humoral immunity and is performed by two types of antibodies, IgM, which are the first responders and highly effective at neutralizing viruses, but they only last for few weeks, and are the protagonists of the acute infection. The second, called IgG, are produced indefinitely. The presence of IgM in the blood of the host is used to test for acute infection, whereas IgG indicates an infection happened sometime in the past and is indicated as chronic infection.

Antibodies can continue to be an effective defense mechanism even after viruses enter the host cell. A protein called TRIM21, can attach to the antibodies on the surface of the virus particle, this promotes the subsequent destruction of the virus by the enzymes of the cell’s proteosome system.

A second defense of vertebrates against viruses is called cell-mediate 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 recognizes a suspicious viral fragment there, the host cell is destroyed by ‘killer T’ cells and the virus-specific T-cells proliferate.

Macrophages are specialized cells at the antigen presentation. The production of interferon is an important host defense 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 neighbors.

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. This is known as escape mutation as the viral epitopes escape recognition by the host immune response. These persistent viruses evade immune control by sequestration, blockade of antigen presentation, cytokine resistance, evasion of natural killer cells activities, escape from apoptosis, and antigenic shifts. Other viruses, called neurotropic viruses are disseminated by neural spread where the immune system may be unable to reach them.

Oncoviruses are an established cause of cancer in humans and other species. Viral cancers occur only in a minority of infected people (or animals). Cancer viruses come from a range of virus families, including both RNA and DNA viruses, and so there is no single type of oncovirus (an outdated term originally used for acutely transforming retroviruses). The development of cancer is determined by a variety of factors such as host immunity and mutations in the host. Viruses accepted to cause human cancers include some genotypes of human Papillomavirus, Hepatitis B, virus, Epstein-Barr.

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 vaccinations to provide immunity to infection, and antiviral drugs that selectively interfere with viral replication.

Vaccination is an inexpensive 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 or illness and mortality associated with viral infections such as polio, measles, mumps and rubella. Smallpox infections have been eradicated. Vaccines can consist of live-attenuated or killed viruses, or viral proteins called antigens. 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 immunocompromised, because in these people, the weakened virus can cause the original disease. Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine. Subunit vaccines are safe for immunocompromised patients because they cannot cause the disease. 

Antiviral drugs are often nucleoside analogues, fake DNA building-blocks, which viruses mistakenly incorporate into their genomes during replication. The life cycle of the virus is then halted because the newly synthesized DNA is inactive. This is because these analogues lack the hydroxyl groups, which, along with phosphorus atoms, link together to form the strong “backbone” of the DNA molecule. This is called DNA chain termination. Examples of nucleoside analogues are acyclovir for Herpes simplex virus infections and lamivudine for HIV and Hepatitis B virus infections. Acyclovir is one of the oldest and most frequently prescribed antiviral drugs. Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the HIV-1 protease for it to become fully infectious. There is a large class of drugs called protease inhibitors that inactivate this enzyme.

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. There is now an effective treatment that uses the nucleoside analogue drug ribavirin combined with interferon. For chronic carriers of the hepatitis B virus has been developed a new treatment that uses a similar strategy with the drug lamivudine.

Thanks for Reading

Mariarosaria M.

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Source:

Wikipedia Encyclopedia.