The Future of hllv treatment This finding has exciting implications for developing a accine against AIDS. Before this, scientists have been un New discoveries of how HIV works continue to fuel re- successful in trying to produce a harmless strain of AIDs search on devising ways to counter HIV. For example, sci- that can elicit an effective immune response. The Aus- entists are testing drugs and vaccines that act on HIV re- tralian strain with the defective nef gene has the potential to ceptors, researching the possibility of blocking CCR5, and be used in a vaccine that would arm the immune system poking for defects in the structures of HIv receptors inin- against this and other strains of HIv dividuals that are infected with hiv but have not devel- Another potential application of this discovery is its use oped AIDS. Figure 33. 8 summarizes some of the recent de- in developing drugs that inhibit HiV proteins that speed velopments and discoveries virus replication. It seems that the protein produced from the nef gene is one of these critical HIv proteins, because Combination Drug Therapy viruses with defective forms of nef do not reproduce, as seen in the cases of the six australians. Research is cur- A variety of drugs inhibit HIV in the test tube. These in- rently underway to develop a drug that targets the nef clude AZt and its analogs(which inhibit virus nucleic acid protein replication)and protease inhibitors (which inhibit the leavage of the large polyproteins encoded by gag, poll, and env genes into functional capsid, enzyme, and envelope seg Chemokines and CAF ments). When combinations of these drugs were adminis- In the laboratory, chemicals called chemokines appear to tered to people with HIV in controlled studies, their condi- inhibit HIV infection by binding to and blocking the tion improved. A combination of a protease inhibitor and CCR5 and CXCR4 coreceptors. As you might expect, peo- two AZT analog drugs entirely eliminated the HIV virus ple long infected with the Hiv virus who have not devel- from many of the patients'bloodstreams. Importantly, all oped AIDS prove to have high levels of chemokines in their of these patients began to receive the drug therapy within blood. three months of contracting the virus, before their bodies The search for HIV-inhibiting chemokines is intense had an opportunity to develop tolerance to any one of Not all results are promising. Researchers report that in them. Widespread use of this combination therapy ha their tests, the levels of chemokines were not different be- cut the U.S. AIDS death rate by three-fourths since its in- tween patients in which the disease was not progressing troduction in the mid-1990s, from 49,000 AIDS deaths in and those in which it was rapidly progressing More 1995 to 36,000 in 1996, and just over 10,000 in 1999 romising, levels of another factor called CAF(CD8+ cell Unfortunately, this sort of combination therapy does antiviral factor)are different between these two groups. Re not appear to actually succeed in eliminating HIV from searchers have not yet succeeded in isolating CAF, which the body. While the virus disappears from the blood- seems not to block receptors that HIV uses to gain entry to stream, traces of it can still be detected in lymph tissue of cells, but, instead, to prevent replication of the virus once it the patients. When combination therapy is discontinued, has infected the cells. Research continues on the use of virus levels in the bloodstream once again rise. Because chemokines in treatments for HIV infection, either in of demanding therapy schedules and many side effects, creasing the amount of chemokines or disabling the ccr long-term combination therapy does not seem a promis- receptor. However, promising research on CAF suggests ing approach. that it may be an even better target for treatment and pre vention of aids Using a Defective HIV Gene to Combat AIds One problem with using chemokines as drugs is that they are also involved in the inflammatory response of Recently, five people in Australia who are HIV-positive but the immune system. The function of chemokines is to at have not developed AIDS in 14 years were found to have all tract white blood cells to areas of infection. Chemokines received a blood transfusion from the same HIV-positive work beautifully in small amounts and in local areas, but person, who also has not developed AIDS. This led scien- chemokines in mass numbers can cause an inflammatory tists to believe that the strain of virus transmitted to these response that is worse than the original infection. Injec- people has some sort of genetic defect that prevents it from tions of chemokines may hinder the immune systems ffectively disabling the human immune system. In subse- ability to respond to local chemokines, or they may even quent research, a defect was found in one of the nine genes trigger an out-of-control inflammatory response. Thus, present in this strain of HiV. This gene is called nef named scientists caution that injection of chemokines could for"negative factor, "and the defective version of nef in the make patients more susceptible to infections, and they HiV strain that infected the six Australians seems to be continue to research other methods of using chemokines missing some pieces. Viruses with the defective gene may to treat AIDS ave reduced reproductive capability, allowing the immune system to keep the virus in check. 672 Part IX Viruses and Simple organism
The Future of HIV Treatment New discoveries of how HIV works continue to fuel research on devising ways to counter HIV. For example, scientists are testing drugs and vaccines that act on HIV receptors, researching the possibility of blocking CCR5, and looking for defects in the structures of HIV receptors in individuals that are infected with HIV but have not developed AIDS. Figure 33.8 summarizes some of the recent developments and discoveries. Combination Drug Therapy A variety of drugs inhibit HIV in the test tube. These include AZT and its analogs (which inhibit virus nucleic acid replication) and protease inhibitors (which inhibit the cleavage of the large polyproteins encoded by gag, poll, and env genes into functional capsid, enzyme, and envelope segments). When combinations of these drugs were administered to people with HIV in controlled studies, their condition improved. A combination of a protease inhibitor and two AZT analog drugs entirely eliminated the HIV virus from many of the patients’ bloodstreams. Importantly, all of these patients began to receive the drug therapy within three months of contracting the virus, before their bodies had an opportunity to develop tolerance to any one of them. Widespread use of this combination therapy has cut the U.S. AIDS death rate by three-fourths since its introduction in the mid-1990s, from 49,000 AIDS deaths in 1995 to 36,000 in 1996, and just over 10,000 in 1999. Unfortunately, this sort of combination therapy does not appear to actually succeed in eliminating HIV from the body. While the virus disappears from the bloodstream, traces of it can still be detected in lymph tissue of the patients. When combination therapy is discontinued, virus levels in the bloodstream once again rise. Because of demanding therapy schedules and many side effects, long-term combination therapy does not seem a promising approach. Using a Defective HIV Gene to Combat AIDS Recently, five people in Australia who are HIV-positive but have not developed AIDS in 14 years were found to have all received a blood transfusion from the same HIV-positive person, who also has not developed AIDS. This led scientists to believe that the strain of virus transmitted to these people has some sort of genetic defect that prevents it from effectively disabling the human immune system. In subsequent research, a defect was found in one of the nine genes present in this strain of HIV. This gene is called nef, named for “negative factor,” and the defective version of nef in the HIV strain that infected the six Australians seems to be missing some pieces. Viruses with the defective gene may have reduced reproductive capability, allowing the immune system to keep the virus in check. This finding has exciting implications for developing a vaccine against AIDS. Before this, scientists have been unsuccessful in trying to produce a harmless strain of AIDS that can elicit an effective immune response. The Australian strain with the defective nef gene has the potential to be used in a vaccine that would arm the immune system against this and other strains of HIV. Another potential application of this discovery is its use in developing drugs that inhibit HIV proteins that speed virus replication. It seems that the protein produced from the nef gene is one of these critical HIV proteins, because viruses with defective forms of nef do not reproduce, as seen in the cases of the six Australians. Research is currently underway to develop a drug that targets the nef protein. Chemokines and CAF In the laboratory, chemicals called chemokines appear to inhibit HIV infection by binding to and blocking the CCR5 and CXCR4 coreceptors. As you might expect, people long infected with the HIV virus who have not developed AIDS prove to have high levels of chemokines in their blood. The search for HIV-inhibiting chemokines is intense. Not all results are promising. Researchers report that in their tests, the levels of chemokines were not different between patients in which the disease was not progressing and those in which it was rapidly progressing. More promising, levels of another factor called CAF (CD8+ cell antiviral factor) are different between these two groups. Researchers have not yet succeeded in isolating CAF, which seems not to block receptors that HIV uses to gain entry to cells, but, instead, to prevent replication of the virus once it has infected the cells. Research continues on the use of chemokines in treatments for HIV infection, either increasing the amount of chemokines or disabling the CCR5 receptor. However, promising research on CAF suggests that it may be an even better target for treatment and prevention of AIDS. One problem with using chemokines as drugs is that they are also involved in the inflammatory response of the immune system. The function of chemokines is to attract white blood cells to areas of infection. Chemokines work beautifully in small amounts and in local areas, but chemokines in mass numbers can cause an inflammatory response that is worse than the original infection. Injections of chemokines may hinder the immune system’s ability to respond to local chemokines, or they may even trigger an out-of-control inflammatory response. Thus, scientists caution that injection of chemokines could make patients more susceptible to infections, and they continue to research other methods of using chemokines to treat AIDS. 672 Part IX Viruses and Simple Organisms
① Combination Therapy Vaccine or ug Ther Replication tat or rev rotating defective ne AzT 5-P vpr Replication Envelope Critical protein (3)Blocking Receptors 4)Disabling Receptors (5Blocking Replication with CAF CD4 CXCR4 Chemokine CXCR4 blocking receptor CD4+ cell FIGURE 33. 8 Research is currently underway to develop new treatments for HIV. Among them are these five: (1)Combination therapy involves using two drugs, AZT to block replication of the virus and protease inhibitors to block the production of critical viral proteins. (2)Using a defective form of the viral gene nef, scientists may be able to construct an HIV vaccine. Also, drug therapy that inhibits nef's protein product is being tested. ()Other research focuses on the use of chemokine chemicals to block receptors(CXCR4 and CCR5), thereby disabling the antiviral factor which acts inside the CD4+ T cell, may be able to block replication of HI, tors may also be possible. (5) Lastly, CAF,an mechanism HIV uses to enter CD4+ Tcells. (4) Producing mutations that will disable rece Disabling Receptors African-American populations(2%), and absent in African A 32-base-pair deletion in the gene that codes for the CCr and Asian populations. Treatment for AIDS involving dis- receptor appears to block HIV infection. Individuals at high ruption of CCR5 looks promising, as research indicates that people live perfectly well with risk of hiv infection who are homozygous for this mutation or disable CCR5 are being sought in numerous laboratories out do not seem to develop AIDS. In one study of 1955 people scientists found no individuals who were infected and ho us for the mutated allele. the allele A cure for AIDS is not yet in hand, but many new more common in Caucasian populations(10 to 11%)than in approaches look promising Chapter 33 Viruses 673
Disabling Receptors A 32-base-pair deletion in the gene that codes for the CCR5 receptor appears to block HIV infection. Individuals at high risk of HIV infection who are homozygous for this mutation do not seem to develop AIDS. In one study of 1955 people, scientists found no individuals who were infected and homozygous for the mutated allele. The allele seems to be more common in Caucasian populations (10 to 11%) than in African-American populations (2%), and absent in African and Asian populations. Treatment for AIDS involving disruption of CCR5 looks promising, as research indicates that people live perfectly well without CCR5. Attempts to block or disable CCR5 are being sought in numerous laboratories. A cure for AIDS is not yet in hand, but many new approaches look promising. Chapter 33 Viruses 673 Blocking Receptors gp120 Viral RNA HIV CD4 CCR5 or Chemokine CXCR4 blocking receptor Mutated coreceptor Disabling Receptors CCR5 or CXCR4 Blocking Replication with CAF Replication CAF 3 4 5 CD4 CD4+ cell Envelope proteins tat or rev gag pol vif vpr vpu env nef Replication AZT Protease inhibitors Capsid proteins Replication proteins Critical protein nef protein inhibitor Vaccine incorporating defective nef 1 Combination Therapy Vaccine or Drug Therapy 2 HIV RNA FIGURE 33.8 Research is currently underway to develop new treatments for HIV. Among them are these five: (1) Combination therapy involves using two drugs, AZT to block replication of the virus and protease inhibitors to block the production of critical viral proteins. (2) Using a defective form of the viral gene nef, scientists may be able to construct an HIV vaccine. Also, drug therapy that inhibits nef’s protein product is being tested. (3) Other research focuses on the use of chemokine chemicals to block receptors (CXCR4 and CCR5), thereby disabling the mechanism HIV uses to enter CD4 T cells. (4) Producing mutations that will disable receptors may also be possible. (5) Lastly, CAF, an antiviral factor which acts inside the CD4 T cell, may be able to block replication of HIV.
33.4 Nonliving infectious agents are responsible for many human diseases Disease viruses each type: Type A flu virus causes most of the serious flu epidemics in humans, and also occurs in mammals and Humans have known and feared diseases caused by viruses birds. Type B and Type C viruses, with narrower host for thousands of years. Among the diseases that viruses ranges, are restricted to humans and rarely cause serious cause(table 33. 1)are influenza, smallpox, infectious hepati- health problems tis,yellow fever, polio, rabies, and AIDS, as well as many other diseases not as well known. In addition, viruses have Subtypes. Different strains of flu virus, called subtypes, en implicated in some cancers and leukemias. For many differ in their protein spikes. One of these proteins, autoimmune diseases, such as multiple sclerosis and hemagglutinin(H)aids the virus in gaining access to the rheumatoid arthritis, and for diabetes, specific viruses have cell interior. The other, neuraminidase(N) helps the been found associated with certain cases. In view of their daughter virus break free of the host cell once virus repli- effects, it is easy to see why the late Sir Peter Medawar, cation has been completed. Parts of the H molecule con- Nobel laureate in Physiology or Medicine, wrote, "A virus tain "hot spots"that display an unusual tendency to is a piece of bad news wrapped in protein. "Viruses not hange as a result of mutation of the virus rNa during only cause many human diseases, but also cause major imprecise replication. Point mutations cause changes in losses in agriculture, forestry, and in the productivity of these spike proteins in 1 of 100,000 viruses during the natural ecosystems course of each generation. These highly variable seg ments of the H molecule are targets against which the Influenza ody's antibodies are directed. The high variability of these targets improves the reproductive capacity of the Perhaps the most lethal virus in human history has beer virus and hinders our ability to make perfect vaccines the influenza virus, Some 22 million americans and eure Because of accumulating changes in the h and n mole peans died of flu within 18 months in 1918 and 1919, an as- cules, different flu vaccines are required to protect against different subtypes. Type A flu viruses are cur rently classified into 13 distinct H subtypes and 9 distinct Types. Flu viruses are animal retroviruses. An individ- N subtypes, each of which requires a different vaccine to ual flu virus resembles a rod studded with spikes com- protect against infection. Thus, the type A virus that posed of two kinds of protein(figure 33.9). There are caused the Hong Kong flu epidemic of 1968 has type 3 H three general"types"of flu virus, distinguished by their molecules and type 2 N molecules, and is called capsid(inner membrane) protein, which is different for A(H3N2 Envelope(outer Capsid (inner protein lipid membrane) membrane) Neuraminidase Tagalog Coils of rna FIGURE 33.9 The influenza virus. (a) TEM of the so-called "bird flu"influenza virus, A(H5N1), which first infected humans in Hong Kong in 1997. ( Diagram of an influenza virus. The coiled RNA has been revealed by cutting through the outer lipid-rich envelope, with its two kinds of projecting spikes, and the inner protein capsid. 674 Part IX Viruses and Simple organism
Disease Viruses Humans have known and feared diseases caused by viruses for thousands of years. Among the diseases that viruses cause (table 33.1) are influenza, smallpox, infectious hepatitis, yellow fever, polio, rabies, and AIDS, as well as many other diseases not as well known. In addition, viruses have been implicated in some cancers and leukemias. For many autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis, and for diabetes, specific viruses have been found associated with certain cases. In view of their effects, it is easy to see why the late Sir Peter Medawar, Nobel laureate in Physiology or Medicine, wrote, “A virus is a piece of bad news wrapped in protein.” Viruses not only cause many human diseases, but also cause major losses in agriculture, forestry, and in the productivity of natural ecosystems. Influenza Perhaps the most lethal virus in human history has been the influenza virus. Some 22 million Americans and Europeans died of flu within 18 months in 1918 and 1919, an astonishing number. Types. Flu viruses are animal retroviruses. An individual flu virus resembles a rod studded with spikes composed of two kinds of protein (figure 33.9). There are three general “types” of flu virus, distinguished by their capsid (inner membrane) protein, which is different for each type: Type A flu virus causes most of the serious flu epidemics in humans, and also occurs in mammals and birds. Type B and Type C viruses, with narrower host ranges, are restricted to humans and rarely cause serious health problems. Subtypes. Different strains of flu virus, called subtypes, differ in their protein spikes. One of these proteins, hemagglutinin (H) aids the virus in gaining access to the cell interior. The other, neuraminidase (N) helps the daughter virus break free of the host cell once virus replication has been completed. Parts of the H molecule contain “hot spots” that display an unusual tendency to change as a result of mutation of the virus RNA during imprecise replication. Point mutations cause changes in these spike proteins in 1 of 100,000 viruses during the course of each generation. These highly variable segments of the H molecule are targets against which the body’s antibodies are directed. The high variability of these targets improves the reproductive capacity of the virus and hinders our ability to make perfect vaccines. Because of accumulating changes in the H and N molecules, different flu vaccines are required to protect against different subtypes. Type A flu viruses are currently classified into 13 distinct H subtypes and 9 distinct N subtypes, each of which requires a different vaccine to protect against infection. Thus, the type A virus that caused the Hong Kong flu epidemic of 1968 has type 3 H molecules and type 2 N molecules, and is called A(H3N2). 674 Part IX Viruses and Simple Organisms 33.4 Nonliving infectious agents are responsible for many human diseases. Envelope (outer lipid membrane) Capsid (inner protein membrane) Hemagglutinin Coils of RNA Neuraminidase (a) (b) FIGURE 33.9 The influenza virus. (a) TEM of the so-called “bird flu” influenza virus, A(H5N1), which first infected humans in Hong Kong in 1997. (b) Diagram of an influenza virus. The coiled RNA has been revealed by cutting through the outer lipid-rich envelope, with its two kinds of projecting spikes, and the inner protein capsid
Human viral dis Patho Vector/Epidemiology AIDS Destroys immune defenses, resulting in death by infection or can acer Over 33 milli n cases worldwide by 1998 Chicken pox Human herpes- H Spread through contact with infected individuals. No cure. virus 3(varicella Rarely fatal. Vaccine approved in U.S. in early 199 zoster) Ebola Filoviruses Acute hemorrhagic fever; virus attacks connective tissue, leading to massive hemorrhaging and death. Peak mortali is 50-90% if the disease goes untreated. Outbreaks confined to local regions of central Africa H H H Highly infectious through contact with infected body fluids. (HB pproximately 1% of U.S. popu Herpes simplex H Fever blisters; spread primarily through contact with irus(HSV infected saliva. Very prevalent Exhibits latency-the disease can be dormant for Influenza Influenza viruses Humans, ducks Historically a major killer(22 million died in 18 months in ng to new fl Measles Paramyxoviruses Humans Extremely contagious through contact with infected individuals. Vaccine available. Usually contracted in childhood, when it is not serious; more dangerous to adults Mononucleosis Epstein-Barr Humans Spread through contact with infected saliva May last several virus(eBv weeks; common in young adults. No cure. Rarely fatal Paramyxovirus Spread through contact with infected saliva. Vaccine available; rarely fatal. No cure. Pneumonia Influenza virus Humans Acute infection of the lungs, often fatal without treatment. polio Poliovirus Acute viral infection of the CNS that can lead to paralysis and is often fatal. Prior to the development of Salk's vaccine in 1954, 60,000 people a year contracted the disease in the U.S. alone Rabies Rhabdovirus wild and domestic Canidae An acute viral encephalomyelitis transmitted by the bite of an infected animal. Fatal if untreated coyotes, bats, and raccoons Variola virus Historically a major killer; the last recorded case of smallpox only exists in two research was in 1977. A worldwide vaccination campaign wiped out labs---may be eliminated the disease complete Yellow fever Flavivirus Spread from individual to individual by mosquito bites; a notable cause of death during the construction of the Panama Canal. If untreated, this disease has a peak mortality rate of 60% Importance of Recombination. The greatest problem (that is, worldwide epidemics) that occurred in the last in combating flu viruses arises not through mutation, but century, by producing drastic shifts in H N combina through recombination. Viral genes are readily reas ions. The"killer flu"of 1918, A(HINI), killed 40 mil- sorted by genetic recombination, sometimes putting to- lion people. The Asian flu of 1957, A(H2N2), killed over gether novel combinations of H and N spikes unrecog 100,000 Americans. The Hong Kong flu of 1968, sizable by human antibodies specific for the old A(H3N2), infected 50 million people in the United States configuration. Viral recombination of this kind seems to alone, of which 70,000 died have been responsible for the three major flu pandemics Chapter 33 Viruses 675
Importance of Recombination. The greatest problem in combating flu viruses arises not through mutation, but through recombination. Viral genes are readily reassorted by genetic recombination, sometimes putting together novel combinations of H and N spikes unrecognizable by human antibodies specific for the old configuration. Viral recombination of this kind seems to have been responsible for the three major flu pandemics (that is, worldwide epidemics) that occurred in the last century, by producing drastic shifts in H N combinations. The “killer flu” of 1918, A(H1N1), killed 40 million people. The Asian flu of 1957, A(H2N2), killed over 100,000 Americans. The Hong Kong flu of 1968, A(H3N2), infected 50 million people in the United States alone, of which 70,000 died. Chapter 33 Viruses 675 Table 33.1 Important Human Viral Diseases Disease Pathogen Reservoir Vector/Epidemiology AIDS HIV STD Destroys immune defenses, resulting in death by infection or cancer. Over 33 million cases worldwide by 1998. Chicken pox Human herpes- Humans Spread through contact with infected individuals. No cure. virus 3 (varicella- Rarely fatal. Vaccine approved in U.S. in early 1995. zoster) Ebola Filoviruses Unknown Acute hemorrhagic fever; virus attacks connective tissue, leading to massive hemorrhaging and death. Peak mortality is 50–90% if the disease goes untreated. Outbreaks confined to local regions of central Africa. Hepatitus B Hepatitis B virus Humans Highly infectious through contact with infected body fluids. (viral) (HBV) Approximately 1% of U.S. population infected. Vaccine available, no cure. Can be fatal. Herpes Herpes simplex Humans Fever blisters; spread primarily through contact with virus (HSV) infected saliva. Very prevalent worldwide. No cure. Exhibits latency—the disease can be dormant for several years. Influenza Influenza viruses Humans, ducks Historically a major killer (22 million died in 18 months in 1918–19); wild Asian ducks, chickens, and pigs are major reservoirs. The ducks are not affected by the flu virus, which shuffles its antigen genes while multiplying within them, leading to new flu strains. Measles Paramyxoviruses Humans Extremely contagious through contact with infected individuals. Vaccine available. Usually contracted in childhood, when it is not serious; more dangerous to adults. Mononucleosis Epstein-Barr Humans Spread through contact with infected saliva. May last several virus (EBV) weeks; common in young adults. No cure. Rarely fatal. Mumps Paramyxovirus Humans Spread through contact with infected saliva. Vaccine available; rarely fatal. No cure. Pneumonia Influenza virus Humans Acute infection of the lungs, often fatal without treatment. Polio Poliovirus Humans Acute viral infection of the CNS that can lead to paralysis and is often fatal. Prior to the development of Salk’s vaccine in 1954, 60,000 people a year contracted the disease in the U.S. alone. Rabies Rhabdovirus Wild and domestic Canidae An acute viral encephalomyelitis transmitted by the bite of (dogs, foxes, wolves, an infected animal. Fatal if untreated. coyotes), bats, and raccoons Smallpox Variola virus Formerly humans, now Historically a major killer; the last recorded case of smallpox only exists in two research was in 1977. A worldwide vaccination campaign wiped out labs—may be eliminated the disease completely. Yellow fever Flavivirus Humans, mosquitoes Spread from individual to individual by mosquito bites; a notable cause of death during the construction of the Panama Canal. If untreated, this disease has a peak mortality rate of 60%
It is no accident that new strains of flu usually originate in the far east. The most common hosts of influenza virus are ducks, chickens, and pigs, which in Asia often live in close proximity to each other and to humans. Pigs are sub ject to infection by both bird and human strains of the rus,and individual animals are often simultaneously in fected with multiple strains. This creates conditions favor ing genetic recombination between strains, producing new combinations of H and N subtypes. The Hong Kong flu, for example, arose from recombination between A(H3N8) from ducks] and A(H2N2)[from humans]. The new strain of influenza, in this case A(H3N2), then passed back to hu- mans, creating an epidemic because the human population has never experienced that H N combination before FIGURE 33.10 a potentially deadly new strain of flu virus emerged in The Ebola virus. This virus, with a fatality rate that can exceed Hong Kong in 1997, A(H5N1). Unlike all previous in % appears sporadically in West Africa. Health professionals are stances of new flu strains, A(H5N1) passed to humans di- scrambling to identify the natural host of the virus, which is rectly from birds, in this case chickens. A(HSN1) was first unknown, so they can devise strategies to combat transmission of identified in chickens in 1961, and in the spring of 1997 devastated flocks of chickens in Hong Kong. Fortunately this strain of flu virus does not appear to spread easily from person to person, and the number of human infections by associated with rodents. The hantavirus is transmitted to (H5N1)remains small. Public health officials remain con- humans through rodent fecal contamination in areas of cerned that the genes of A(H5N1) could yet mix with those human habitation. Although hantavirus has been known for of a human strain to create a new strain that could spread some period of time, this particular outbreak was attributed widely in the human population, and to prevent this or to the presence of an unusually large rodent population in dered the killing of all 1. 2 million chickens in Hong Kong the area following a higher than normal amount of rainfall in1997 the previous winter. Emerging Viruses Viruses and cancer Sometimes viruses that originate in one organism pass to Through epidemiological studies and research, scientists have established a link between some viral infections and pansion is deadly to the new host. HIV, for example, arose the subsequent development of cancer. Examples include chimpanzees and relatively recently passed to humans the association between chronic hepatitis B infections and Influenza is fundamentally a bird virus. Viruses that origi the development of liver cancer and the development of nate in one organism and then pass to another and cause cervical carcinoma following infections with certain strains sease are called emerging viruses and represent a con- siderable threat in an age when airplane travel potentially tribute to about 15% of all human cancer cases worldwide allows in fected individuals to move about the world Viruses are capable of altering the growth properties of quickly, spreading an infection. human cells they infect by triggering the expression of Among the most lethal of emerging viruses are a collec- oncogenes(cancer-causing genes). Certain viruses can ei- ion of filamentous viruses arising in central Africa that ther activate host proto-oncogenes(see chapter 18)or cause severe hemorrhagic fever. With lethality rates in ex- ring in viral oncogenes that become inc corporated into cess of 50%, these so-called filoviruses are among the most host genome. Virus-induced cancer is not simply a matter lethal infectious diseases known. One, Ebola virus(figure of infection. The disease involves complex interactions with 33.10), has exhibited lethality rates in excess of 90% in iso- cellular genes and requires a series of events in order to de lated outbreaks in central Africa. The outbreak of Ebola velop virus in the summer of 1995 in Zaire killed 245 people out of 316 infected-a mortality rate of 78%. The latest out Viruses are responsible for some of the most lethal break occurred in Gabon, West Africa, in February 1996 diseases of humans. Some of the most serious examples The natural host of ebola is unknown are viruses that have transferred to humans from some Another type of emerging virus caused a sudden out other host Influenza, a bird virus, has been responsible break of a hemorrhagic-type infection in the southwestern for the most devastating epidemics in human history United States in 1993. This highly fatal disease was soon Newly emerging viruses such as Ebola have received ttributed to the hantavirus, a single-stranded rNa virus considerable public attention. 676 Part IX Viruses and Simple organism
It is no accident that new strains of flu usually originate in the far east. The most common hosts of influenza virus are ducks, chickens, and pigs, which in Asia often live in close proximity to each other and to humans. Pigs are subject to infection by both bird and human strains of the virus, and individual animals are often simultaneously infected with multiple strains. This creates conditions favoring genetic recombination between strains, producing new combinations of H and N subtypes. The Hong Kong flu, for example, arose from recombination between A(H3N8) [from ducks] and A(H2N2) [from humans]. The new strain of influenza, in this case A(H3N2), then passed back to humans, creating an epidemic because the human population has never experienced that H N combination before. A potentially deadly new strain of flu virus emerged in Hong Kong in 1997, A(H5N1). Unlike all previous instances of new flu strains, A(H5N1) passed to humans directly from birds, in this case chickens. A(H5N1) was first identified in chickens in 1961, and in the spring of 1997 devastated flocks of chickens in Hong Kong. Fortunately, this strain of flu virus does not appear to spread easily from person to person, and the number of human infections by A(H5N1) remains small. Public health officials remain concerned that the genes of A(H5N1) could yet mix with those of a human strain to create a new strain that could spread widely in the human population, and to prevent this ordered the killing of all 1.2 million chickens in Hong Kong in 1997. Emerging Viruses Sometimes viruses that originate in one organism pass to another, thus expanding their host range. Often, this expansion is deadly to the new host. HIV, for example, arose in chimpanzees and relatively recently passed to humans. Influenza is fundamentally a bird virus. Viruses that originate in one organism and then pass to another and cause disease are called emerging viruses and represent a considerable threat in an age when airplane travel potentially allows infected individuals to move about the world quickly, spreading an infection. Among the most lethal of emerging viruses are a collection of filamentous viruses arising in central Africa that cause severe hemorrhagic fever. With lethality rates in excess of 50%, these so-called filoviruses are among the most lethal infectious diseases known. One, Ebola virus (figure 33.10), has exhibited lethality rates in excess of 90% in isolated outbreaks in central Africa. The outbreak of Ebola virus in the summer of 1995 in Zaire killed 245 people out of 316 infected—a mortality rate of 78%. The latest outbreak occurred in Gabon, West Africa, in February 1996. The natural host of Ebola is unknown. Another type of emerging virus caused a sudden outbreak of a hemorrhagic-type infection in the southwestern United States in 1993. This highly fatal disease was soon attributed to the hantavirus, a single-stranded RNA virus associated with rodents. The hantavirus is transmitted to humans through rodent fecal contamination in areas of human habitation. Although hantavirus has been known for some period of time, this particular outbreak was attributed to the presence of an unusually large rodent population in the area following a higher than normal amount of rainfall the previous winter. Viruses and Cancer Through epidemiological studies and research, scientists have established a link between some viral infections and the subsequent development of cancer. Examples include the association between chronic hepatitis B infections and the development of liver cancer and the development of cervical carcinoma following infections with certain strains of papillomaviruses. It has been suggested that viruses contribute to about 15% of all human cancer cases worldwide. Viruses are capable of altering the growth properties of human cells they infect by triggering the expression of oncogenes (cancer-causing genes). Certain viruses can either activate host proto-oncogenes (see chapter 18) or bring in viral oncogenes that become incorporated into the host genome. Virus-induced cancer is not simply a matter of infection. The disease involves complex interactions with cellular genes and requires a series of events in order to develop. Viruses are responsible for some of the most lethal diseases of humans. Some of the most serious examples are viruses that have transferred to humans from some other host. Influenza, a bird virus, has been responsible for the most devastating epidemics in human history. Newly emerging viruses such as Ebola have received considerable public attention. 676 Part IX Viruses and Simple Organisms FIGURE 33.10 The Ebola virus. This virus, with a fatality rate that can exceed 90%, appears sporadically in West Africa. Health professionals are scrambling to identify the natural host of the virus, which is unknown, so they can devise strategies to combat transmission of the disease