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Exercise1

病毒学(双语)习题1

一、阅读下述短文,然后回答问题(每个问题8分,中英文均可)

In order to persist and evolve in nature, viruses need a large population of susceptible hosts and an efficient means of spread between these hosts. The normal route is termed horizontal spread. The most common route of entry and exit of viruses is the respiratory route. Following their inhalation, viruses usually infect and replicate in the epithelial cells of the upper and lower respiratory tract (e.g. rhinoviruses, coronaviruses, influenza, para-influenza and respiratory syncytial virus). The viruses produced in these airways exit their host via sneezing and coughing. Many viruses which enter and exit via this route are not 'respiratory viruses' (e.g. chicken pox, measles, German measles). In these cases the virus leaves the respiratory tract to set up infection in other target organs. The oral-gastrointestinal route is used mainly by those viruses responsible for gut infections (rotavirus, Norwalk virus and the enteroviruses, including polio and coxsackie viruses). Vast numbers of virus particles can be excreted in fecal material (e.g. in the order of 1012particles g-1), facilitating the easy spread of these viruses in conditions of poor sanitation. Thus, the drinking of contaminated water and consumption of contaminated shellfish or other food prepared by unhygienic food handlers are ways in which these viruses are spread.

Whilst the skin normally provides an impenetrable barrier to virus invasion, infectious viruses can enter following trauma to the skin. This may be from the bite of an animal vector (e.g. rabies via an infected canine, yellow fever via an infected mosquito). HIV, hepatitis B and hepatitis C may be transmitted by the injection of blood or blood products either in the form of a blood transfusion, a needle-stick injury, or by intravenous drug abuse.

Sexual transmission of viruses is an important route for the spread of HSV, the papilloma viruses and HIV.

Viruses may also be transmitted vertically- that is, from mother to offspring via the placenta, during childbirth, or in breast milk. Examples are rubella virus (German measles) and cytomegalovirus (CMV), acquired by the mother during pregnancy and transmitted to the developing embryo, often leading to severe congenital abnormalities and/or spontaneous abortion. Some viral infections, for example, HSV infections, if acquired in utero or during birth can present as an acute disease syndrome in the neonate. In the case of HIV and hepatitis B transmission, the neonate may be born with an asymptomatic infection, the virus persisting in a carrier state and developing into disease much later.

Questions:

1.What does horizontal transmission mean? Please give examples.

2.The skin normally provides good protection against virus infection. But sometimes viruses can infect

through the skin. Please explain.

3.What is the vertical transmission of a virus? Please give examples.

As obligate intracellular parasites with very restricted genetic-coding capacity viruses rely heavily on utilizing the metabolic machinery of the cell for their replication. It was therefore considered by many that the concept of selective toxicity was an unattainable goal and that interference with viral replication would

always bring unacceptable damage to the host. Viruses by definition are resistant to the action of antibiotics. In the last decade a series of discoveries based on our increasing knowledge of the viral replication cycle and the specific gene products encoded by viruses have resulted in a number of successful antiviral agents being prescribed. However, some still have a level of toxicity which, while acceptable for some diseases (e.g. AIDS), would not be tolerated for less severe diseases.

Chemotherapeutic agents fall into three broad groups. Virucides directly inactivate viruses (e.g. detergents, solvents), antivirals strive to inhibit viral multiplication but not host-cell metabolism and immunomodulating agents attempt to enhance the immune response against viruses (e.g. administration of interleukins). In this chapter antivirals will be discussed.

Viral replication requires the virus to pass through a number of stages which are common to all viruses: attachment and penetration, uncoating of the nucleic acid, transcription and translation, replication of nucleic acids and release of mature progeny.

To date, most antivirals are directed at inhibiting one of the steps of the virus infection cycle, although the most common target is interference with nucleic acid metabolism by using many nucleoside analogs. Several compounds that interfere with influenza affect the disassembly of particles by blocking a virus protein complex that acts as an ion channel. Many viruses produce a virus-specific protease to process their proteins and this has been targeted in the search to develop an inhibitor of HIV. A series of inhibitors of picornaviruses act by directly binding to the virion capsid, blocking the interaction between the virion and the receptor on the cell surface that facilitates its entry and disassembly.

In the early days, most new antiviral compounds were discovered in an empirical fashion. Chemists would produce a wide range of, for example, nucleoside analogs, originally in many cases as anti-cancer drugs, which were tested in tissue culture to determine their antiviral activities. However, with our knowledge of the molecular basis of virus replication, the availability of the entire nucleotide sequences of virus genomes and the three-dimensional protein structure derived from X-ray diffraction analysis, compounds can be designed to interact with specific targets involved in the replicative cycle of viruses. In practice the most useful targets are virus-induced enzymes which often have properties different to those of the counterpart enzymes induced by the host cell (e.g. thymidine kinase, DNA polymerase, reverse transcriptase and protease). When the enzyme can be crystalized and its three-dimensional structure determined the synthesis of appropriate molecules to interact with particular sites on that enzyme can be determined. However, future antiviral compounds should lack toxicity and should be able to be produced cheaply from available precursors. The chance of a wide range of new products appearing is therefore remote.

Questions:

4.Why it was considered by many that the concept of selective toxicity was an unattainable goal for

virus infection?

5.Describe the groups of chemotherapeutic agents based on their action mechanisms.

6.What are the most useful targets in practice for the development of antiviral compounds?

二、将下述短文译成中文(52分)

1. Influenza A(H1N1) pandemic preparedness

In the past, influenza pandemics have resulted in increased morbidity and mortality and great social disruption. In the 20th century, the most severe influenza pandemic occurred in 1918 -1919 and caused an estimated 40–50 million deaths world wide. Current epidemiological models project that a pandemic could result in 2 to 7.4 million deaths globally.

If an influenza pandemic were to occur today, we could expect:

the pandemic virus to spread rapidly due to the high level of global traffic;

vaccines, antiviral agents and antibiotics to treat secondary infections to be in short supply, with a period of several months before any vaccine becomes available;

medical facilities to be overwhelmed with demands to care for both influenza and non-inflenza patients; widespread illness to result in sudden and potentially significant shortages of personnel to provide essential community services.

Continuous global surveillance of influenza is key to the early detection of a virus with pandemic potential. WHO has a network of more than 120 National Influenza Centres in over 90 countries that monitor influenza activity and isolate influenza viruses in every region of the world. National Influenza Centres will report the detection of an “unusual” influenza virus immediately to the WHO Global Influenza Programme and one of the five WHO Collaborating Centres. Rapid detection of unusual influenza outbreaks, isolation of viruses with pandemic potential and immediate alert to WHO by national authorities is critical to a timely and efficient response.

Contingency planning for an event that will occur at an undetermined time in the future is difficult, particularly in the face of limited resources and other urgent problems and priorities. However, there are two main reasons to invest in pandemic preparedness

Improving public health infrastructure through pandemic planning has immediate and lasting benefits, increasing overall response capacity for all threats to public health.

Strengthening coordination mechanisms at national and international levels contributes to better global preparedness and response for disasters and public health emergencies. (30分)

2.Enteroviruses are small viruses. The enteroviruses that occur in the United States include coxsackieviruses and echoviruses. Polioviruses are also included in the term “enterovirus,” but they have been eradicated from the United States by vaccination. In all, more than 60 different types of enteroviruses have been identified. In Illinois and the United States, enterovirus infections are second only to the “common cold.” It has been estimated that at least 10 million to 15 million persons in the Un ited States develop some sort of enteroviral illness each year. Immunity can occur after infection with one of these viruses. However, the immunity is only to one of the enteroviruses. It does not protect against infection from the others. Anyone can become infected and ill with these viruses. Infants, children and adolescents are more likely to become ill than are adults. Adults are more likely to be immune to specific enteroviruses than are younger persons.

Enteroviruses can be found in respiratory secretions, such as saliva, sputum or nasal secretions, and in the feces of infected persons. Persons may become infected by direct contact with secretions from an infected person, or by contact with contaminated objects such as drinking and eating utensils. Transmission also may occur if an infected person coughs or sneezes directly in the face of another person. These viruses can be transmitted by contact with feces, such as when persons changing diapers of infants and toddlers do not wash their hands thoroughly. Persons with no symptoms of illness who are infected with an enterovirus can infect other persons who may or may not become ill after they become infected.(22分)