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18.2 Viruses, viroids, and prions are formidable pathogens in ...

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<strong>18.2</strong> <strong>Viruses</strong>, <strong>viroids</strong>, <strong>and</strong> <strong>prions</strong> <strong>are</strong> <strong>formidable</strong> <strong>pathogens</strong> <strong>in</strong> animals <strong>and</strong> plants<br />

Section Vocabulary Vacc<strong>in</strong>e - A harmless variant or derivative of a pathogen that stimulates a host’s immune system<br />

to mount defenses aga<strong>in</strong>st the pathogen.<br />

Viroid - A plant pathogen composed of molecules of naked circular RNA only several hundred<br />

nucleotides long.<br />

Prion - An <strong>in</strong>fectious form of prote<strong>in</strong> that may <strong>in</strong>crease <strong>in</strong> number by convert<strong>in</strong>g related prote<strong>in</strong>s<br />

to more <strong>prions</strong>.<br />

Viral Diseases <strong>in</strong> Animals The l<strong>in</strong>k between a viral <strong>in</strong>fection <strong>and</strong> the symptoms it produces is often obscure. <strong>Viruses</strong> may<br />

damage or kill cells by caus<strong>in</strong>g the release of hydrolytic enzymes from lysosomes. Some viruses<br />

cause <strong>in</strong>fected cells to produce tox<strong>in</strong>s that lead to disease symptoms, <strong>and</strong> some have molecular<br />

components that <strong>are</strong> toxic, such as envelope prote<strong>in</strong>s. How much damage a virus causes depends<br />

partly on the ability of the <strong>in</strong>fected tissue to regenerate by cell division. People usually recover<br />

completely from colds because the epithelium of the respiratory tract, which the viruses <strong>in</strong>fect,<br />

can efficiently repair itself. In contrast, damage <strong>in</strong>flicted by poliovirus to mature nerve cells is<br />

permanent, because these cells do not divide <strong>and</strong> usually cannot be replaced. Many of the<br />

temporary symptoms associated with viral <strong>in</strong>fections, such as fever <strong>and</strong> aches, actually result<br />

from the body’s own efforts at defend<strong>in</strong>g itself aga<strong>in</strong>st <strong>in</strong>fection.<br />

The immune system is a complex <strong>and</strong> critical part of the body’s natural defenses. The immune<br />

system is also the basis for the major medical tool for prevent<strong>in</strong>g viral <strong>in</strong>fections—vacc<strong>in</strong>es.<br />

Vacc<strong>in</strong>es <strong>are</strong> harmless variants or derivatives of pathogenic microbes that stimulate the immune<br />

system to mount defenses aga<strong>in</strong>st the actual pathogen. Vacc<strong>in</strong>ation has eradicated smallpox, at<br />

one time a devastat<strong>in</strong>g scourge <strong>in</strong> many parts of the world. The viruses that cause smallpox,<br />

polio, <strong>and</strong> measles <strong>in</strong>fect only humans. This very narrow host range was critical to the successful<br />

effort of the World Health Organization to eradicate smallpox; similar worldwide vacc<strong>in</strong>ation<br />

campaigns currently <strong>are</strong> under way to eradicate the other two viruses as well. Effective vacc<strong>in</strong>es<br />

<strong>are</strong> also available aga<strong>in</strong>st rubella, mumps, hepatitis B, <strong>and</strong> a number of other viral diseases.<br />

Although vacc<strong>in</strong>es can prevent certa<strong>in</strong> viral illnesses, medical technology can do little, at present,<br />

to cure most viral <strong>in</strong>fections once they occur. The antibiotics that help us recover from bacterial<br />

<strong>in</strong>fections <strong>are</strong> powerless aga<strong>in</strong>st viruses. Antibiotics kill bacteria by <strong>in</strong>hibit<strong>in</strong>g enzyme–catalyzed<br />

processes specific to the <strong>pathogens</strong>, but viruses have few or no enzymes of their own. However,<br />

a few drugs effectively combat certa<strong>in</strong> viruses. Most antiviral drugs resemble nucleosides <strong>and</strong> as<br />

a result <strong>in</strong>terfere with viral nucleic acid synthesis. One such drug is acyclovir, which impedes<br />

herpesvirus reproduction by <strong>in</strong>hibit<strong>in</strong>g the viral polymerase that synthesizes viral DNA. Similarly,<br />

azidothymid<strong>in</strong>e (AZT) curbs HIV reproduction by <strong>in</strong>terfer<strong>in</strong>g with the synthesis of DNA by reverse<br />

transcriptase. In the past ten years, much effort has gone <strong>in</strong>to develop<strong>in</strong>g drugs aga<strong>in</strong>st HIV.<br />

Currently, multidrug treatments, sometimes called “cocktails,” have been found to be most<br />

effective. Such a regimen commonly <strong>in</strong>cludes a comb<strong>in</strong>ation of two nucleoside mimics <strong>and</strong> a<br />

protease <strong>in</strong>hibitor, which <strong>in</strong>terferes with an enzyme required for assembly of virus particles.<br />

Emerg<strong>in</strong>g <strong>Viruses</strong> <strong>Viruses</strong> that appear suddenly or that suddenly come to the attention of medical scientists <strong>are</strong><br />

often referred to as emerg<strong>in</strong>g viruses. HIV, the AIDS virus, is a classic example: This virus<br />

appe<strong>are</strong>d <strong>in</strong> San Francisco <strong>in</strong> the early 1980s, seem<strong>in</strong>gly out of nowhere. The deadly Ebola virus,<br />

recognized <strong>in</strong>itially <strong>in</strong> 1976 <strong>in</strong> central Africa, is one of several emerg<strong>in</strong>g viruses that cause<br />

hemorrhagic fever, an often fatal syndrome characterized by fever, vomit<strong>in</strong>g, massive bleed<strong>in</strong>g,<br />

<strong>and</strong> circulatory system collapse. A number of other dangerous new viruses cause encephalitis,<br />

<strong>in</strong>flammation of the bra<strong>in</strong>. One example is the West Nile virus, which appe<strong>are</strong>d for the first time<br />

<strong>in</strong> North America <strong>in</strong> 1999 <strong>and</strong> has spread to all 48 contiguous states <strong>in</strong> the U.S.<br />

An even more recent viral disease to emerge is severe acute respiratory syndrome (SARS), which<br />

first appe<strong>are</strong>d <strong>in</strong> southern Ch<strong>in</strong>a <strong>in</strong> November 2002 (Figure 18.11a). Dur<strong>in</strong>g a global outbreak<br />

from November 2002 to July 2003, about 8,000 people were known to be <strong>in</strong>fected, of whom<br />

more than 700 subsequently died. Researchers quickly identified the agent caus<strong>in</strong>g SARS as a<br />

coronavirus, a virus with a s<strong>in</strong>gle–str<strong>and</strong>ed RNA genome (class IV) that was not previously known<br />

to cause disease <strong>in</strong> humans (Figure 18.11b).<br />

From where <strong>and</strong> how do such viruses burst on the human scene, giv<strong>in</strong>g rise to previously r<strong>are</strong> or<br />

unknown diseases? Three processes contribute to the emergence of viral diseases. First, the<br />

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<strong>18.2</strong> <strong>Viruses</strong>, <strong>viroids</strong>, <strong>and</strong> <strong>prions</strong> <strong>are</strong> <strong>formidable</strong> <strong>pathogens</strong> <strong>in</strong> animals <strong>and</strong> plants<br />

mutation of exist<strong>in</strong>g viruses is a major source of these new diseases. RNA viruses tend to have an<br />

unusually high rate of mutation because errors <strong>in</strong> replicat<strong>in</strong>g their RNA genomes <strong>are</strong> not<br />

corrected by proofread<strong>in</strong>g. Some mutations enable exist<strong>in</strong>g viruses to evolve <strong>in</strong>to new genetic<br />

varieties (stra<strong>in</strong>s) that can cause disease <strong>in</strong> <strong>in</strong>dividuals who had developed immunity to the<br />

ancestral virus. Flu epidemics, for <strong>in</strong>stance, <strong>are</strong> caused by new stra<strong>in</strong>s of <strong>in</strong>fluenza virus<br />

genetically different enough from earlier stra<strong>in</strong>s that people have little immunity to them.<br />

Another source of new viral diseases is the spread of exist<strong>in</strong>g viruses from one host species to<br />

another. Scientists estimate that about three–quarters of new human diseases orig<strong>in</strong>ate <strong>in</strong> other<br />

animals. For example, hantavirus is common <strong>in</strong> rodents, especially deer mice. The population of<br />

deer mice <strong>in</strong> the southwestern United States exploded <strong>in</strong> 1993 after unusually wet weather<br />

<strong>in</strong>creased the rodents′ food supply. Many people who <strong>in</strong>haled dust conta<strong>in</strong><strong>in</strong>g traces of ur<strong>in</strong>e <strong>and</strong><br />

feces from <strong>in</strong>fected mice became <strong>in</strong>fected with hantavirus, <strong>and</strong> dozens died. The source of the<br />

SARS–caus<strong>in</strong>g virus was still undeterm<strong>in</strong>ed as of spr<strong>in</strong>g 2004, although c<strong>and</strong>idates <strong>in</strong>clude the<br />

exotic animals found <strong>in</strong> food markets <strong>in</strong> Ch<strong>in</strong>a. And early 2004 brought reports of the first cases<br />

of people <strong>in</strong> southeast Asia <strong>in</strong>fected with a flu virus previously seen only <strong>in</strong> birds. If this virus<br />

evolves so that it can spread easily from person to person, the potential for a major human<br />

outbreak is significant. Indeed, evidence is strong that the flu p<strong>and</strong>emic of 1918–1919, which<br />

killed about 40 million people, orig<strong>in</strong>ated <strong>in</strong> birds.<br />

F<strong>in</strong>ally, the dissem<strong>in</strong>ation of a viral disease from a small, isolated population can lead to<br />

widespread epidemics. For <strong>in</strong>stance, AIDS went unnamed <strong>and</strong> virtually unnoticed for decades<br />

before it began to spread around the world. In this case, technological <strong>and</strong> social factors,<br />

<strong>in</strong>clud<strong>in</strong>g affordable <strong>in</strong>ternational travel, blood transfusions, sexual promiscuity, <strong>and</strong> the abuse of<br />

<strong>in</strong>travenous drugs, allowed a previously r<strong>are</strong> human disease to become a global scourge.<br />

Thus, emerg<strong>in</strong>g viruses <strong>are</strong> generally not new; rather, they <strong>are</strong> exist<strong>in</strong>g viruses that mutate,<br />

spread to new host species, or dissem<strong>in</strong>ate more widely <strong>in</strong> the current host species. Changes <strong>in</strong><br />

host behavior or environmental changes can <strong>in</strong>crease the viral traffic responsible for emerg<strong>in</strong>g<br />

diseases. For example, new roads through remote <strong>are</strong>as can allow viruses to spread between<br />

previously isolated human populations. Another problem is the destruction of forests to exp<strong>and</strong><br />

cropl<strong>and</strong>, an environmental disturbance that br<strong>in</strong>gs humans <strong>in</strong>to contact with other animals that<br />

may host viruses capable of <strong>in</strong>fect<strong>in</strong>g humans.<br />

Viral Diseases <strong>in</strong> Plants More than 2,000 types of viral diseases of plants <strong>are</strong> known, <strong>and</strong> together they account for an<br />

estimated loss of $15 billion annually worldwide due to agricultural <strong>and</strong> horticultural crop<br />

destruction. Common symptoms of viral <strong>in</strong>fection <strong>in</strong>clude bleached or brown spots on leaves <strong>and</strong><br />

fruits, stunted growth, <strong>and</strong> damaged flowers or roots, all tend<strong>in</strong>g to dim<strong>in</strong>ish the yield <strong>and</strong><br />

quality of crops (Figure 18.12).<br />

Plant viruses have the same basic structure <strong>and</strong> mode of replication as animal viruses. Most plant<br />

viruses discovered thus far, <strong>in</strong>clud<strong>in</strong>g tobacco mosaic virus (TMV), have an RNA genome. Many<br />

have a rod–shaped capsid, like TMV (see Figure 18.4a); others have a polyhedral capsid.<br />

Plant viral diseases spread by two major routes. In the first route, called horizontal transmission,<br />

a plant is <strong>in</strong>fected from an external source of the virus. Because the <strong>in</strong>vad<strong>in</strong>g virus must get past<br />

the plant’s outer protective layer of cells (the epidermis), the plant becomes more susceptible to<br />

viral <strong>in</strong>fections if it has been damaged by w<strong>in</strong>d, <strong>in</strong>jury, or <strong>in</strong>sects. Insects pose a double threat,<br />

because they can also act as carriers of viruses, transmitt<strong>in</strong>g disease from plant to plant. Farmers<br />

<strong>and</strong> gardeners may transmit plant viruses <strong>in</strong>advertently on prun<strong>in</strong>g shears <strong>and</strong> other tools. The<br />

other route of viral <strong>in</strong>fection is vertical transmission, <strong>in</strong> which a plant <strong>in</strong>herits a viral <strong>in</strong>fection<br />

from a p<strong>are</strong>nt. Vertical transmission can occur <strong>in</strong> asexual propagation (for example, by tak<strong>in</strong>g<br />

cutt<strong>in</strong>gs) or <strong>in</strong> sexual reproduction via <strong>in</strong>fected seeds.<br />

Once a virus enters a plant cell <strong>and</strong> beg<strong>in</strong>s reproduc<strong>in</strong>g, viral components can spread throughout<br />

the plant by pass<strong>in</strong>g through plasmodesmata, the cytoplasmic connections that penetrate the<br />

walls between adjacent plant cells (see Figure 6.28). Prote<strong>in</strong>s encoded by viral genes <strong>are</strong> capable<br />

of alter<strong>in</strong>g the diameter of plasmodesmata to allow passage of viral prote<strong>in</strong>s or genomes.<br />

Scientists have not yet devised cures for most viral plant diseases. So their efforts <strong>are</strong> focused<br />

largely on reduc<strong>in</strong>g the <strong>in</strong>cidence <strong>and</strong> transmission of such diseases <strong>and</strong> on breed<strong>in</strong>g varieties of<br />

crop plants that <strong>are</strong> relatively resistant to certa<strong>in</strong> viruses.<br />

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<strong>18.2</strong> <strong>Viruses</strong>, <strong>viroids</strong>, <strong>and</strong> <strong>prions</strong> <strong>are</strong> <strong>formidable</strong> <strong>pathogens</strong> <strong>in</strong> animals <strong>and</strong> plants<br />

Viroids <strong>and</strong> Prions: The<br />

Simplest Infectious Agents As small <strong>and</strong> simple as viruses <strong>are</strong>, they dwarf another class of <strong>pathogens</strong>: <strong>viroids</strong>. These <strong>are</strong><br />

circular RNA molecules, only several hundred nucleotides long, that <strong>in</strong>fect plants. One viroid<br />

disease has killed over 10 million coconut palms <strong>in</strong> the Philipp<strong>in</strong>es. Viroids do not encode<br />

prote<strong>in</strong>s but can replicate <strong>in</strong> host plant cells, app<strong>are</strong>ntly us<strong>in</strong>g cellular enzymes. These small RNA<br />

molecules seem to cause errors <strong>in</strong> the regulatory systems that control plant growth, <strong>and</strong> the<br />

symptoms typically associated with viroid diseases <strong>are</strong> abnormal development <strong>and</strong> stunted<br />

growth.<br />

An important lesson from <strong>viroids</strong> is that a s<strong>in</strong>gle molecule can be an <strong>in</strong>fectious agent that spreads<br />

a disease. But <strong>viroids</strong> <strong>are</strong> nucleic acid, whose ability to be replicated is well known. Even more<br />

surpris<strong>in</strong>g is the evidence for <strong>in</strong>fectious prote<strong>in</strong>s, called <strong>prions</strong>, which appear to cause a number<br />

of degenerative bra<strong>in</strong> diseases <strong>in</strong> various animal species. These diseases <strong>in</strong>clude scrapie <strong>in</strong> sheep;<br />

mad cow disease, which has plagued the European beef <strong>in</strong>dustry <strong>in</strong> recent years; <strong>and</strong><br />

Creutzfeldt–Jakob disease <strong>in</strong> humans, which has caused the death of some 125 British people <strong>in</strong><br />

the past decade. Prions <strong>are</strong> most likely transmitted <strong>in</strong> food, as <strong>in</strong> the consumption by people of<br />

prion–laden beef from cattle with mad cow disease. Two characteristics of <strong>prions</strong> <strong>are</strong> especially<br />

alarm<strong>in</strong>g. First, <strong>prions</strong> <strong>are</strong> very slow–act<strong>in</strong>g agents; the <strong>in</strong>cubation period until symptoms appear<br />

is around ten years. Second, <strong>prions</strong> <strong>are</strong> virtually <strong>in</strong>destructible; they <strong>are</strong> not destroyed or<br />

deactivated by heat<strong>in</strong>g to normal cook<strong>in</strong>g temperatures. To date, there is no known cure for<br />

prion diseases, <strong>and</strong> the only hope for develop<strong>in</strong>g effective treatments lies <strong>in</strong> underst<strong>and</strong><strong>in</strong>g the<br />

mechanism of <strong>in</strong>fection.<br />

How can a prote<strong>in</strong>, which cannot replicate itself, be a transmissible pathogen? Accord<strong>in</strong>g to the<br />

lead<strong>in</strong>g hypothesis, a prion is a misfolded form of a prote<strong>in</strong> normally present <strong>in</strong> bra<strong>in</strong> cells. When<br />

the prion gets <strong>in</strong>to a cell conta<strong>in</strong><strong>in</strong>g the normal form of the prote<strong>in</strong>, the prion converts the<br />

normal prote<strong>in</strong> to the prion version (Figure 18.13). In this way, <strong>prions</strong> may repeatedly trigger<br />

cha<strong>in</strong> reactions that <strong>in</strong>crease their numbers. This model, first proposed <strong>in</strong> the early 1980s, is now<br />

widely accepted.<br />

1. Describe two ways a preexist<strong>in</strong>g virus can become an emerg<strong>in</strong>g virus.<br />

a. Mutations can lead to a new stra<strong>in</strong> of a virus that can no longer be recognized by the immune<br />

system, even if an animal has been exposed to the orig<strong>in</strong>al stra<strong>in</strong>; a virus can jump from one<br />

species to a new host; <strong>and</strong> a r<strong>are</strong> virus can spread if a population becomes less isolated.<br />

2. Comp<strong>are</strong> horizontal versus vertical transmission of viruses <strong>in</strong> plants.<br />

a. In horizontal transmission, a plant is <strong>in</strong>fected from an external source of virus, which could enter<br />

through a break <strong>in</strong> the plant’s epidermis due to damage by <strong>in</strong>sects or other animals. In vertical<br />

transmission, a plant <strong>in</strong>herits viruses from its p<strong>are</strong>nt either via <strong>in</strong>fected seeds (sexual<br />

reproduction) or via an <strong>in</strong>fected cutt<strong>in</strong>g (asexual reproduction).<br />

3. Why does the long <strong>in</strong>cubation period of <strong>prions</strong> <strong>in</strong>crease their danger as a cause of human disease?<br />

a. A source of <strong>in</strong>fection, such as prion–<strong>in</strong>fected cattle, may show no symptoms for many years. Beef<br />

prep<strong>are</strong>d from such animals before symptoms appear would not be recognized as hazardous <strong>and</strong><br />

could transmit <strong>in</strong>fection to people who eat the meat.<br />

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