Why do prions differ from viruses

Some of the plants they infect include potatoes, cucumbers, tomatoes, chrysanthemums, avocados, and coconut palms. Potatoes infected by a viroid : These potatoes have been infected by the potato spindle tuber viroid PSTV. It is typically spread when infected knives are used to cut healthy potatoes, which are then planted.

Privacy Policy. Skip to main content. Search for:. Prions and Viroids. Prions and Viroids Prions are infectious particles that contain no nucleic acids, and viroids are small plant pathogens that do not encode proteins.

Learning Objectives Describe prions and viroids and their basic properties. An infectious structural variant of a normal cellular protein called PrP prion protein is known to cause spongiform encephalopathies. Prions have been implicated in fatal neurodegenerative diseases, such as kuru in humans and bovine spongiform encephalopathy BSE in cattle.

Loss of motor control and unusual behaviors are common symptoms of individuals with kuru and BSE; symptoms are usually followed by death. Viroids do not have a capsid or outer envelope and can reproduce only within a host cell. Viroids are not known to cause any human diseases, but they are responsible for crop failures and the loss of millions of dollars in agricultural revenue each year. Some of the plants they infect include potatoes, cucumbers, tomatoes, chrysanthemums, avocados, and coconut palms.

Career Connection Virologist Virology is the study of viruses, and a virologist is an individual trained in this discipline. Training in virology can lead to many different career paths.

Virologists are actively involved in academic research and teaching in colleges and medical schools. Some virologists treat patients or are involved in the generation and production of vaccines. They might participate in epidemiologic studies Figure or become science writers, to name just a few possible careers. If you think you may be interested in a career in virology, find a mentor in the field. Many large medical centers have departments of virology, and smaller hospitals usually have virology labs within their microbiology departments.

Volunteer in a virology lab for a semester or work in one over the summer. Discussing the profession and getting a first-hand look at the work will help you decide whether a career in virology is right for you. Section Summary Prions are infectious agents that consist of protein, but no DNA or RNA, and seem to produce their deadly effects by duplicating their shapes and accumulating in tissues.

They are thought to contribute to several progressive brain disorders, including mad cow disease and Creutzfeldt-Jakob disease. Viroids are single-stranded RNA pathogens that infect plants.

Their presence can have a severe impact on the agriculture industry. Prions are responsible for variant Creutzfeldt-Jakob Disease, which has resulted in over human deaths in Great Britain during the last 10 years.

How do humans contract this disease? This prion-based disease is transmitted through human consumption of infected meat. A botanist notices that a tomato plant looks diseased.

How could the botanist confirm that the agent causing disease is a viroid, and not a virus? The botanist would need to isolate any foreign nucleic acids from infected plant cells, and confirm that an RNA molecule is the etiological agent of disease. The botanist would then need to demonstrate that the RNA can infect plant cells without a capsid, and that the RNA replicates, but is not translated to produce proteins.

Clinical treatment with interferons is used to treat viral infections in a few cases e. It responds to intracellular pathogens. They bind to the interferon receptors of both the infected cell itself and its neighbors.

Locally, this triggers a phosphorelay signal pathway that activates several genes that combat virus infection Fig. Interferons also help activate immune system cells, such as NK cells, which selectively destroy virus-infected cells.

These are secreted to neighboring cells, bind to the interferon receptor, and activate various antiviral proteins. P1 kinase blocks protein synthesis by phosphorylating eIF2 an elongation factor. Without ATP and protein synthesis, the virus cannot survive in the host cell. This removes the ATP required as an energy source for viral replication. P1 kinase is also activated and phosphorylates initiation factor eIF2, halting protein synthesis.

The Mx protein assembles into ring structures that surround the viral RNA. This blocks the movement of the RNA polymerase and consequently prevents replication. Different strains of influenza virus differ in their susceptibility to Mx proteins, and conversely, different animals have slightly different Mx proteins.

These variants play a major role in determining both virulence and the transmission of virus between different animals. Interferon alpha was one of the first mammalian proteins to be manufactured via genetic engineering. However, its clinical effects have been disappointing except in a few cases, such as treatment of hepatitis C.

Recent attempts at antiviral therapy have moved away from interferons and focused on using the RNA interference system. Interferons are animal proteins that promote the antiviral response by inducing synthesis of a range of enzymes with specific antiviral activities. The basics of RNA technology were discussed in Chapter 5. Antisense RNA and ribozyme therapy have been proposed for antiviral therapy, but neither has proven effective so far.

RNA interference is a natural defense system used by cells to protect themselves against invasion by RNA viruses. Not surprisingly, many viruses have evolved mechanisms to avoid destruction by RNAi. However, in mammals, administration of artificially synthesized siRNA around 17—21 nucleotides long provokes a strong RNAi response even against viruses with protection mechanisms.

RNAi therapy is especially useful for viruses infecting the respiratory tract. The reason is that the siRNA can be administered easily by inhalation. RNAi is effective against respiratory syncytial virus, influenza, parainfluenza, measles, and several coronaviruses. The siRNA sequences can be screened for effectiveness in cell culture before being used on whole organisms. Phase II clinical trials using siRNA against respiratory syncytial virus are underway, and so far the results are promising.

To achieve this resistance, scientists engineer constructs that generate siRNA internally into transgenic plants see Chapter 15 for details of plant genetic engineering. Several RNA viruses of rice that are spread by insects may cause major crop losses. It can be stimulated by administration of siRNA. Wild-type and transgenic Nicotiana benthamiana plants were then tested against infection with plum pox virus. After 7 days, severe wilting was seen in the wild-type but not the transgenic plants.

Influenza virus , an orthomyxovirus , is an example of a negative-strand single-stranded RNA virus. The flu virus particle contains a segmented genome consisting of eight separate pieces of single-stranded RNA ranging from to nucleotides long. These pieces are each packed into an inner nucleocapsid and are surrounded by an outer envelope Fig. Although the outer membrane is derived from host-cell material, it contains virus-encoded proteins such as neuraminidase, hemagglutinin, and ion channels.

These viral proteins are made on the ribosomes of the infected host cell and are involved in virus recognition and entry into successive host cells.

The hemagglutinin H and neuraminidase N of influenza differ slightly but significantly between strains of flu. These variants are designated by H and N numbers. Thus, the Spanish flu of was H 1 N 1 , and the avian flu presently spreading worldwide is H 5 N 1.

The virulent outbreak of novel avian flu in China in was H 7 N 9. This virus contains segments from several different avian flu strains. Genome analysis confirms increased virulence and implies resistance to amantadine see following discussion. The influenza virus has an outer envelope containing neuraminidase, hemagglutinin, and ion channels. Several individual negative-strand ssRNA molecules are packaged within the outer membrane.

Each strand is coated with nucleocapsid proteins. When a flu virus comes in contact with an appropriate host cell, it is engulfed and ends up inside a vesicle. Both the vesicle and the outer coat of the virus particle are dissolved, releasing the nucleocapsids, which enter the nucleus. The nucleocapsids disassemble inside the nucleus, releasing the RNA molecules Fig. Replication of the influenza RNA occurs in the nucleus. Here, the proteins for the new virus particles are made.

After entry into the host cell, the nucleocapsids enter the nucleus before disassembly. There the viral replicase makes positive RNA strands and more negative strands. Because influenza virus has its genes scattered over eight separate molecules of RNA, different strains of flu can trade segments of RNA and form new genetic combinations Fig.

These two mechanisms result in a lot of genetic diversity. Consequently, different strains of flu emerge every couple of years. The changing surface antigens of the virus allow it to avoid immune recognition.

These different flu strains vary greatly in their apparent virulence. However, this depends as much on the immune history of the human population as on genetic changes in the virus. If two different influenza strains infect the same host cell, the genomes of both will enter the nucleus. When new virus particles are formed, some nucleocapsids from strain 1 may be packaged with strain 2, and vice versa.

Thus, complete ssRNA molecules from different influenza strains may be reshuffled to generate new assortments. Such reshuffling more often happens in pigs and birds than in human hosts.

Influenza viruses fall into two major groups: influenza A and B. Mutation of both A and B causes annual epidemics due to slow antigenic drift. Influenza B is largely restricted to humans and has less genetic variation. As a result, influenza A gives rise to severe but less common epidemics due to reassortment of viruses from different hosts during mixed infections. The Spanish flu of — was the worst influenza A pandemic so far and is estimated to have killed around 50 million people more than World War I.

Will there be another major flu pandemic soon? The major threat seems to be the successive versions of avian flu emerging in Asia. Relatively few humans catch these viruses by direct transmission from birds. The real danger is that these avian viruses will mutate to become transmissible from person to person. Amantadine is a tricyclic amine that binds to the M2 protein, one of the transmembrane ion channels found in the outer envelope of influenza A virus.

M2 is not expressed by influenza B, and consequently, amantadine works only against type A influenza. Amantadine blocks the M2 ion channel, and this stops entry of protons, which prevents uncoating of the virus particle Fig.

Thus, entry of the virus is prevented. Amantadine must be given very early in infection. Amantadine was the first specific antiviral agent to be discovered, although its mode of action was only elucidated later.

The amantadine molecule blocks ions from passing though the M2 channel in the virus coat, thus preventing uncoating and RNA molecule release. These inhibitors are analogs of N -acetylneuraminic acid.

Neuraminidase normally cleaves this from the virus receptor, allowing progeny virus particles to be released. If neuraminidase is inhibited, progeny virus is trapped in infected cells. Resistance can arise due to mutations in the N protein; for example, HY changing His to Tyr results in resistance to oseltamivir but not to zanamivir. Influenza is an extremely common viral infection of humans and some other animals.

Its genome consists of eight pieces of RNA of negative complementarity. As a result, it shows a high rate of both mutation and recombination. Very few drugs are available to treat influenza. Most AIDS patients die of opportunistic infections. These infections are seen only in patients with defective immune systems and are caused by assorted viruses, bacteria, protozoans, and fungi that are normally relatively harmless but may attack if host defenses are down. In addition, without immune surveillance, cancers caused by other viruses or somatic mutations often grow out of control.

HIV infects white blood cells belonging to the immune system, the T cells. The CD4 protein is found on the surface of many T cells, where it acts as an important receptor during the immune response see Chapter 6. The gp protein in the outer envelope of HIV is a glycoprotein with a molecular weight of kDa. It recognizes and binds to CD4, which is needed for entry of the virus. HIV particles are coated with gp, which recognizes the T cells of the immune system.

The viral glycoprotein gp binds to protein CD4, on the surface of the T cell. The viral particle is then taken into the T cell, where it takes over the cellular machinery to produce more virus. The CD4 protein is also found on the surface of some other immune system cells—the monocytes and macrophages. HIV does not seriously harm these two cell types, but the cells become reservoirs to spread the virus to more T cells. The damage to the T cells is most critical to immune function.

Once HIV has entered the T cell, the DNA form of the retrovirus genome integrates into the host chromosome and begins to express virus genes. Viral proteins are manufactured on host ribosomes. In particular, the HIV envelope protein, gp, is made in large amounts and inserts into the T-cell membrane. The gp on the surface of infected T cells binds to the CD4 protein on other T cells. Consequently, several T cells clump together and fuse Fig. The giant, multiple cell soon dies.

As they gradually die off, the immune response fades away over a 5- to year period. Damage to T cells cripples the immune response, leaving the body open to other infections. Once HIV has entered the T cell, gp is made in large amounts and is inserted into the host cell membrane. T cells with gp in their membranes bind to other T cells via the CD4 receptor, which causes the cells to fuse. The process continues until large clumps of T cells form.

These cells soon die, crippling the immune system. The entry of HIV into T cells requires binding of virus to both the CD4 protein and one of several chemokine receptors, which act as co-receptors. The chemokine receptors are membrane proteins with seven trans -membrane segments. They bind chemokines , a group of approximately 50 small messenger peptides that activate the white blood cells of the immune system and attract them to the site of infections.

Mutations in CCR5 are largely responsible for the small proportion of the population who are naturally resistant to HIV infection. In addition, if these individuals are infected, the disease progresses much more slowly. Heterozygotes are mildly protected and show slower progression, in accord with the lower levels of CCR5 protein on the surfaces of their T cells. Conceivably, the defects in CCR5 were selected by providing resistance against the bubonic plague.

Presumably, these alterations cause variations in the level of CCR5 protein expressed. Receptors that take up important molecules into animal cells are often the targets for viruses. It is quite possible for the same host cell protein to be used as a receptor by unrelated infectious agents, including both viruses and bacteria.

Which receptors are used by smallpox or other poxviruses is still unknown. Scientists are presently trying to identify the functions of the various receptors on immune cells in the hope of understanding how viruses exploit them for their own use. Entry of HIV into target cells requires co-receptors. HIV mutates at a rate of approximately one base per genome per cycle of replication.

Even within a single patient, HIV exists as a swarm of closely related variants known as a quasi-species. Consequently, strains of HIV resistant to individual drugs appear at a relatively high frequency. In practice, this problem may be partially overcome by simultaneous treatment with several drugs that hit different targets. HIV infections could be stopped at the following steps: 1 at the cell surface, competing molecules could prevent virus attachment; 2 enzyme inhibitors may block the action of reverse transcriptase; 3 integration of the viral genome could be prevented; 4 transcription and translation could be blocked; 5 finally, blocking virion packaging and budding would protect other cells from becoming infected.

Although AZT is incorporated more readily by the viral reverse transcriptase than by most host-cell DNA polymerases, it is not completely specific. In particular, it is toxic to bone marrow cells B cells , which are another part of the immune system. Mutations in the HIV reverse transcriptase may cause resistance to base analogs. For example, Met41Leu i. Two examples of chain terminators are azidothymidine AZT and acyclovir, which replace thymine and guanine, respectively.

The entire deoxyribose ring is altered in acyclovir. In both cases, the analogs are incorporated into DNA during the reverse transcriptase reaction. Certain drugs that do not bind at the active site can also inhibit reverse transcriptase. They bind to the enzyme at a separate site, relatively close to the active site. This distorts the structure of reverse transcriptase and inhibits its activity.

Unfortunately, mutations that alter the NNRTI binding site occur quite frequently, and they give rise to resistant reverse transcriptase enzyme. These drugs are therefore generally used in combination with nucleoside analogs.