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Part a shows the structure of the influenza virus, which is icosahedral with a viral envelope. Neuraminidase and hemagglutinin are embedded in the envelope. Part b shows that Tamiflu prevents the step in influenza infection in which virions leave the cell.
(a) Tamiflu inhibits a viral enzyme called neuraminidase (NA) found in the influenza viral envelope. (b) Neuraminidase cleaves the connection between viral hemagglutinin (HA), also found in the viral envelope, and glycoproteins on the host cell surface. Inhibition of neuraminidase prevents the virus from detaching from the host cell, thereby blocking further infection. (credit a: modification of work by M. Eickmann)

By far, the most successful use of antivirals has been in the treatment of the retrovirus HIV, which causes a disease that, if untreated, is usually fatal within 10–12 years after infection. Anti-HIV drugs have been able to control viral replication to the point that individuals receiving these drugs survive for a significantly longer time than the untreated.

Anti-HIV drugs inhibit viral replication at many different phases of the HIV replicative cycle ( [link] ). Drugs have been developed that inhibit the fusion of the HIV viral envelope with the plasma membrane of the host cell (fusion inhibitors), the conversion of its RNA genome into double-stranded DNA (reverse transcriptase inhibitors), the integration of the viral DNA into the host genome (integrase inhibitors), and the processing of viral proteins (protease inhibitors).

The illustration shows the steps in the HIV life cycle. In step 1, gp120 glycoproteins in the viral envelope attach to a CD4 receptor on the host cell membrane. The glycoproteins then attached to a co-receptor, CCR5 or CXCR4, and the viral envelope fuses with the cell membrane. HIV RNA, reverse transcriptase, and other viral proteins are released into the host cell. Viral DNA is formed from RNA by reverse transcriptase. Viral DNA is then transported across the nuclear membrane, where it integrates into the host DNA. New viral RNA is made; it is used as genomic RNA and to make viral proteins. New viral RNA and proteins move to the cell surface and a new, immature HIV forms. The virus matures when a protease releases individual HIV proteins.
HIV, an enveloped, icosahedral virus, attaches to the CD4 receptor of an immune cell and fuses with the cell membrane. Viral contents are released into the cell, where viral enzymes convert the single-stranded RNA genome into DNA and incorporate it into the host genome. (credit: NIAID, NIH)

When any of these drugs are used individually, the high mutation rate of the virus allows it to easily and rapidly develop resistance to the drug, limiting the drug’s effectiveness. The breakthrough in the treatment of HIV was the development of HAART, highly active anti-retroviral therapy, which involves a mixture of different drugs, sometimes called a drug “cocktail.” By attacking the virus at different stages of its replicative cycle, it is much more difficult for the virus to develop resistance to multiple drugs at the same time. Still, even with the use of combination HAART therapy, there is concern that, over time, the virus will develop resistance to this therapy. Thus, new anti-HIV drugs are constantly being developed with the hope of continuing the battle against this highly fatal virus.

Everyday connection

Applied virology

The study of viruses has led to the development of a variety of new ways to treat non-viral diseases. Viruses have been used in gene therapy    . Gene therapy is used to treat genetic diseases such as severe combined immunodeficiency (SCID), a heritable, recessive disease in which children are born with severely compromised immune systems. One common type of SCID is due to the lack of an enzyme, adenosine deaminase (ADA), which breaks down purine bases. To treat this disease by gene therapy, bone marrow cells are taken from a SCID patient and the ADA gene is inserted. This is where viruses come in, and their use relies on their ability to penetrate living cells and bring genes in with them. Viruses such as adenovirus, an upper respiratory human virus, are modified by the addition of the ADA gene, and the virus then transports this gene into the cell. The modified cells, now capable of making ADA, are then given back to the patients in the hope of curing them. Gene therapy using viruses as carrier of genes (viral vectors), although still experimental, holds promise for the treatment of many genetic diseases. Still, many technological problems need to be solved for this approach to be a viable method for treating genetic disease.

Another medical use for viruses relies on their specificity and ability to kill the cells they infect. Oncolytic viruses are engineered in the laboratory specifically to attack and kill cancer cells. A genetically modified adenovirus known as H101 has been used since 2005 in clinical trials in China to treat head and neck cancers. The results have been promising, with a greater short-term response rate to the combination of chemotherapy and viral therapy than to chemotherapy treatment alone. This ongoing research may herald the beginning of a new age of cancer therapy, where viruses are engineered to find and specifically kill cancer cells, regardless of where in the body they may have spread.

A third use of viruses in medicine relies on their specificity and involves using bacteriophages in the treatment of bacterial infections. Bacterial diseases have been treated with antibiotics since the 1940s. However, over time, many bacteria have developed resistance to antibiotics. A good example is methicillin-resistant Staphylococcus aureus (MRSA, pronounced “mersa”), an infection commonly acquired in hospitals. This bacterium is resistant to a variety of antibiotics, making it difficult to treat. The use of bacteriophages specific for such bacteria would bypass their resistance to antibiotics and specifically kill them. Although phage therapy    is in use in the Republic of Georgia to treat antibiotic-resistant bacteria, its use to treat human diseases has not been approved in most countries. However, the safety of the treatment was confirmed in the United States when the U.S. Food and Drug Administration approved spraying meats with bacteriophages to destroy the food pathogen Listeria. As more and more antibiotic-resistant strains of bacteria evolve, the use of bacteriophages might be a potential solution to the problem, and the development of phage therapy is of much interest to researchers worldwide.

Section summary

Viruses cause a variety of diseases in humans. Many of these diseases can be prevented by the use of viral vaccines, which stimulate protective immunity against the virus without causing major disease. Viral vaccines may also be used in active viral infections, boosting the ability of the immune system to control or destroy the virus. A series of antiviral drugs that target enzymes and other protein products of viral genes have been developed and used with mixed success. Combinations of anti-HIV drugs have been used to effectively control the virus, extending the lifespans of infected individuals. Viruses have many uses in medicines, such as in the treatment of genetic disorders, cancer, and bacterial infections.

Questions & Answers

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Chinaza
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Every time someone flushes a toilet in the apartment building, the person begins to jumb back automatically after hearing the flush, before the water temperature changes. Identify the types of learning, if it is classical conditioning identify the NS, UCS, CS and CR. If it is operant conditioning, identify the type of consequence positive reinforcement, negative reinforcement or punishment
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Source:  OpenStax, Biology 9-11 grades. OpenStax CNX. Mar 10, 2015 Download for free at https://legacy.cnx.org/content/col11766/1.2
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