Viral Host Range

Most viruses can infect a single species or even only certain cells within an organism. The major limiting factor in host range is the need for the attachment proteins of the virus to bind to specific receptors on the surface of the host. Another less important limitation is that each virion needs different cellular factors and machinery in order to replicate. Some viruses, however, especially those that cause zoonoses, can multiply in widely divergent species. For example, the West Nile virus that has infected more than 1000 people in 2002 in the United States is primarily a disease of birds that have been bitten by infected mosquitoes. The virus can also infect a wide variety of animals.

Viruses can have their host range modified when two virions that differ in their genome infect the same cell. One modification, called phenotypic mixing, results from an exchange of protein coats. The other modification, called genetic reassort-ment, stems from an exchange of genetic information.

Exchange of Protein Coats—Phenotypic Mixing

Animal cells sometimes can be infected simultaneously by more than one virus, even when the viruses are from different genera. As the different viruses synthesize their different protein coats and replicate their nucleic acids in such multiply-infected cells, an exchange of protein coats can occur in a phenomenon termed phenotypic mixing (figure 14.16). Since the host range of any virus is determined in large part by its coat protein, a virus that was once unable to infect a certain cell type may gain the ability to do so with its new coat. Thus, its host range can be expanded by this mechanism. Once inside the cell, however, the viral nucleic acid codes for its original coat protein and not the one that it wore when it infected the cell. Therefore, the virions that exit the cell cannot infect the same cell type that was just infected. They return to their original host range. Phenotypic mixing can occur among viruses of the same or different genera. The rhabdo-, herpes-, retro-, and paramyxoviruses can undergo phenotypic mixing among themselves.

How this phenomenon works can be shown using this example of two retroviruses, one of which normally infects mice

Nucleic acid

Replication of nucleic acid and synthesis of protein coats

Assembly

y Virions

Replication of nucleic acid and synthesis of protein coats

Assembly

Lysis

Phenotypic mixing

Figure 14.16 Phenotypic Mixing The viruses that are released from the lysed cells cannot infect the same type of host cells from which they are released. Rather, they can only infect their original host cells.

and the other, chickens (figure 14.17). However, both retroviruses can infect duck cells. When both retroviruses infect the same cells, some of the progeny of the viruses exchange their outside coats. These new viruses have the host range of the virus from which they derived their coat. Now the virus that normally could only infect chickens can transfer its RNA to mice but not chickens. Conversely, the virus that could only infect mice cells can now infect a variety of birds that previously were resistant. The virus that has gained the ability to infect mice, however, loses this ability after it has multiplied in mice. Now it can only infect chickens. The other virus also loses its ability to infect the alternative host.

362 Chapter 14 Viruses, Prions, and Viroids: Infectious Agents of Animals and Plants Avian retrovirus Mouse retrovirus

362 Chapter 14 Viruses, Prions, and Viroids: Infectious Agents of Animals and Plants Avian retrovirus Mouse retrovirus

Viral Phenotypic Mixing

Mouse virus coat

Mouse virus genome

Avian virus coat

Mouse cell

Chicken cell

Figure 14.17 Phenotypic Mixing of Two Retroviruses When a cell is infected by two different retroviruses, one from a chicken and one from a mouse, exchange of the virus envelopes can occur.The avian virus genome carries the mouse virus coat, and the mouse virus genome is enclosed in the coat of the chicken virus.

Mouse virus coat

Mouse virus genome

Avian virus coat

Mouse cell

Chicken cell

Figure 14.17 Phenotypic Mixing of Two Retroviruses When a cell is infected by two different retroviruses, one from a chicken and one from a mouse, exchange of the virus envelopes can occur.The avian virus genome carries the mouse virus coat, and the mouse virus genome is enclosed in the coat of the chicken virus.

Segmented nucleic acid

Different /viruses

Replication of nucleic acid and synthesis of protein coats

Assembly

Lysis

Genetic reassortment

Figure 14.18 Genetic Reassortment The virion that undergoes genetic reassortment continues to give rise to progeny with the same characteristics.

Genome Exchange in Segmented Viruses

Segmented viruses may alter their properties by genetic reas-sortment (figure 14.18). This phenomenon likely explains how the virulence of the human influenza virus changes so dramatically every 10 to 30 years. These changes result in deadly worldwide epidemics, called pandemics, because the global population does not have antibodies that protect against the new strain of the virus.

A number of different strains of the influenza virus exist, which can be distinguished by the fact that they are specific for infecting different species of animals and birds. The genome of the influenza virus is divided into eight segments of RNA, each containing different genetic information. One of the segments codes for hemagglutinin, a key protein in causing influenza. A human with antibodies against hemagglutinin from the human strain is protected against the disease. If, however, the structure of the hemagglutinin gene changes, then the antibodies will not recognize the protein and will not protect against it. Experimental data suggest that avian and human influenza viruses can simultaneously infect the same cells in a pig, which then serves as a mixing vessel for the 16 RNA segments of the two virions. On occasion, the RNA segment coding for the

14.8 Plant Viruses 363

PERSPECTIVE 14.1 A Whodunit in Molecular Virology

Influenza is a disease that results in symptoms of headache, fever, muscle pain, and coughing.Within a week, these symptoms go away and usually only the elderly or others with a weak immune system die. However, the consequences were much more devastating in two influenza outbreaks in the twentieth century.The "Spanish flu" pandemic of 1918 resulted in more than 20 million deaths around the world, and many of the victims were young adults. In 1997, another deadly influenza virus appeared in Hong Kong; of 18 cases that were diagnosed, 6 were fatal. As in the case of the 1918 "Spanish flu" pandemic, many of the victims were young adults.The Hong Kong virus was transmitted from chickens to humans, but not from humans to humans.Therefore, the epidemic was stopped in its tracks by killing all of the chickens in Hong Kong. Clearly, the influenza virions that caused each of these epidemics must differ from the influenza virions that result in the usual unpleasant but short-term symptoms of influenza.

What made the virions that caused the "Spanish flu" and Hong Kong outbreaks so deadly? By sequencing the RNA genome of the various strains of the influenza virion, some answers are now beginning to emerge.To study the 1918 virions, tissues were obtained from preserved bodies of the 1918 victims who had died from influenza.These included several soldiers and an Eskimo woman whose body was buried in the Alaskan permafrost.The sequencing of the RNA genome focused on the hemagglutinin gene since this gene is very important in determining the virulence of the virion. What investigators found was that the hemagglutinin gene of the "Spanish flu" virion originated by recombination between a swine influenza virion and a human-lineage virion.The end of the protein that binds to receptors on the host cell was encoded by the swine-lineage influenza, whereas the rest of the molecule was encoded by a gene that came from a human-lineage influenza. Apparently the recombination occurred shortly before the pandemic began in 1918 and may have triggered the pandemic.

The highly virulent virion that caused the Hong Kong epidemic in 1997 is a different, more complicated story. By mixing various combinations of the eight segments of the influenza genome, sequencing the segments and determining the virulence of the various strains, investigators determined that several other genes in addition to the hemagglutinin gene were responsible for the virulence of the Hong Kong strain.These genes included the gene encoding the enzyme neuraminidase, which is required for the spread of the virus within the body, and the gene encoding a protein that blocks the synthesis of interferon, a known viral antagonist.

How these changes in the 1918 "Spanish flu"and the Hong Kong 1997 virions created such deadly strains is not totally understood. However, it seems likely that the new strains were able to circumvent the immune response of the host by expressing new proteins, which the body had not encountered before.Thus the immune cells of the body did not recognize the virions and the body was defenseless.We will likely face new killer strains in the future.

avian hemagglutinin is incorporated into the protein coat along with the seven RNA segments from the human strain. Such a strain is still able to infect humans but its avian hemagglutinin makes it a new strain now able to evade the host's antibody defense. This is called an antigenic shift. In addition to the hemagglutinin gene experiencing this major genetic change, the hemagglutinin gene, along with other viral genes, can undergo point mutations that result in relatively small changes in the protein. These changes are termed antigenic drift. Both of these processes will be discussed later in terms of the epidemiology of influenza. ■ antigenic drift and shift, p. 587 ■ antibody, pp. 394, 398 ■ antigen, p. 397 ■ point mutation, p. 193

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Responses

  • willie
    What does it mean by host range viruses?
    7 months ago

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