Martinez J. Hewlett - Basic Virology

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The foundational textbook on the study of virology Basic Virology, 4th Edition This undergraduate-accessible book covers all the foundational topics in virology, including:
The basics of virology Virological techniques Molecular biology Pathogenesis of human viral disease The 4th edition includes new information on the SARS, MERS and COVID-19 coronaviruses, hepatitis C virus, influenza virus, as well as HIV and Ebola. New virological techniques including bioinformatics and advances in viral therapies for human disease are also explored in-depth. The book also includes entirely new sections on metapneumoviruses, dengue virus, and the chikungunya virus.

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Infections with virus do not necessarily lead to any or all symptoms of a disease. The severity of such symptoms is a function of the virus genotype, the amount of virus delivered to the host, and the host's general immune competence – the factors involved with virulence of the infection. The same virus in one individual can lead to an infection with such mild symptoms of disease that they are not recognized for what they are, while infection of another individual can lead to severe symptoms.

Generally, a virus infection results in an effective and lasting immune response. This is described in more detail in Part II, Chapter 7; briefly, the host's immune response (already activated by the presence of viral antigensat any and all sites where virus is replicating) reaches its highest level as clinical signs of the disease manifest.

A full immune response to virus infection requires the maturation of B and T lymphocytes. The maturation of lymphocytes results in the production of short‐lived effector T cells, which kill cells expressing foreign antigens on their surfaces. Another class of effector T cells helps in the maturation of effector B cells for the secretion of antiviral antibodies. Such a process takes several days to a week after stimulation with significant levels of viral antigen. An important part of this immune response is the generation of long‐lived memory lymphocytes to protect against future re‐infection.

In addition to the host's immune response, which takes some time to develop, a number of nonspecific host responses to infection aid in limitation of the infection and contribute to virus clearing. Interferons quickly render sensitive cells resistant to virus infection. Therefore, their action limits or interferes with the ability of the virus to generate high yields of infectious material. Other responses include tissue inflammation, macrophage destruction of infected cells, and increases in body temperature, which can result in suboptimal conditions for virus infection.

Table 2.2Some examples of viral cytopathic effect.

Cytopathic Effect Features Virus
Lysis Lytic infection ultimately results in the loss of integrity of the plasma membrane of the cell. Enteroviruses
Transformation Cells lose their requirement for anchorage to a surface during growth. Also lost is contact inhibition. As a result, cells grow over each other and also grow as a suspension culture. Oncornaviruses
Vacuolization Proliferation of cytoplasmic vacuoles late during the infectious cycle Flaviviruses
Cell fusion Cell–cell fusion leading to the formation of syncytium and polykaryons Paramyxoviruses
Inclusion bodies Densely staining structures within the cytoplasm or nucleus of the cell; often indicates location of viral assembly Various virus families
Apoptosis Programmed cell death, characterized by nuclear events leading to chromosomal disaggregation Lentiviruses

The later stages of infection – virus spread to the next individual

Virus exit is essentially the converse of virus entry at the start of the infection. Now, however, the infected individual is a reservoir of the continuing infection, and symptoms of the disease may have a role in its spread. Some examples should illustrate this simple concept. Infection with a mosquito‐borne encephalitis virus results in high titersof virus in the victim's blood. At the same time, the infected individual's malaise and torpor make him or her an easy mark for a feeding mosquito. In chickenpox(caused by herpes zoster virus, also called varicella zoster virus [ VZV ]), rupture of virus‐filled vesiclesat the surface of the skin can lead to generation of viral aerosols that transmit the infection to others. Similarly, a respiratory disease–causing virus in the respiratory tract along with congestion can lead to sneezing, an effective way to spread an aerosol. A virus such as HIV in body fluids can be transmitted to others via contaminated needles or through unprotected sexual intercourse, especially anal intercourse. Herpesvirus in saliva can enter a new host through a small crack at the junction between the lip and the epidermis.

The later stages of infection – fate of the host

Following a viral or any infectious disease, the host recovers or dies. While many acute infectionsresult in clearance of virus, this does not invariably happen. While infections with influenza virus, cold viruses, polioviruses, and poxviruses resolve with virus clearance, herpesvirus infections result in a lifelong latent infection. During the latent period, no infectious virus is present, but viral genomes are maintained in certain protected cells. Periodically, a (usually) milder recurrence of the disease (reactivation or recrudescence) takes place upon suitable stimulation.

In distinct contrast, measles infection resolves with loss of infectious virus, but a portion of the viral genome can be maintained in neural tissue. This is not a latent infection because the harboring cells can express viral antigens, which lead to lifelong immunity, but infectious virus can never be recovered.

Other lasting types of virus‐induced damage can be much more difficult to establish without extensive epidemiological records. Chronic liver damage due to hepatitis B virus infection is a major factor in hepatic carcinoma. Persistent virus infections can lead to immune dysfunction. Virus infections may also result in the appearance of a disease or syndrome(a set of diagnostic signs and symptoms displayed by an affected individual) years later that has no obvious relation to the initial infection. It has been suggested that diseases such as diabetes mellitus, multiple sclerosis, and rheumatoid arthritis have viral etiologies(ultimate causative factors). Virus factors have also been implicated in instances of other diseases such as cancer and schizophrenia.

QUESTIONS FOR CHAPTER 2

1 A good general rule concerning the replication of RNA viruses is that they require what kind of molecular process?

2 What is the role of a vector in the transmission of a viral infection?

3 It is said that viruses appear to “violate the cell theory” (“cells only arise from preexisting cells”). To which phase of a virus life cycle (growth curve) does this refer? What is the explanation for this phase of the growth curve?

4 Viruses are called “obligate intracellular parasites.” For which step of gene expression do all viruses completely depend on their host cell?

5 Viruses are said to “violate the cell theory,” indicating that there are differences between viruses and cells. The following table lists several features of either viruses or cells or both. Indicate which of these features is true for viruses and which for cells. In each case, write a “Yes” if the feature is true or a “No” if the feature is not true.FeatureCellsVirusesThe genetic information may be RNA rather than DNA.New individuals arise by binary fission of the parent.Proteins are translated from messenger RNAs.New individuals assemble by spontaneous association of subunit structures.

6 At this writing, the avian influenza H5N1 is transmitted from bird to bird, although it may, at some point, mutate to allow transmission from human to human. What feature of virus–host interaction does this characterize?

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