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Discuss mechanisms of viral persistence illustrating your answer with specific examples

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Introduction

Discuss mechanisms of viral persistence illustrating your answer with specific examples Viruses have acquired mechanisms to persist in human hosts even if antiviral drugs are applied to block significant stages in the virus cycle. Strategies are developed by viruses to 'evade, escape and survive' to fight against the host's immune system so that pathogens are able to persists and their purpose can be continued. Usually this type of strategy is employed by the 'hit and stay' viruses and their ultimate aim is to gain long residence in the host's body. Viral reservoirs represent a major problem with terminating infections as the drugs are no longer effective in virus clearance. This could lead to chronic infections, which can be divided into two kinds: The chronic persistent infection and viral latency. In the first type there is continuous replication of the virus from the time of the host being infected primarily and usually associated with virus evolution. The latter type of infection shows a long period of viral suppression as the viruses reduce their expression by displaying only a limited number of viral proteins. Another type of virus strategies are the 'hit and run' infections, which does not often cause persistence but continuous reoccurrence. The viruses are highly infective with the ability to escape to new hosts before the attack of the old infected host's immune system. ...read more.

Middle

Viruses have developed methods to disrupt the synthesis of cytokines and the binding of such molecules to their receptors by encoding substances similar to normal cytokines. Moreover the cytokine signaling pathway is interfered and leads to incorrect signals initiation causing up or down regulation of configuration of the cell receptors. Inhibition of binding to receptors may occur and the normal cytokine pathway is interrupted and the outcome is dysfunctional cytokines on viruses hence another mechanism for immunity evasion. Apoptosis is the mechanism for infected or damaged cells to be programmed to death. Viruses must be able to block this process in some way to prolong viral survival until they have reached their infectious stage and can release its progeny. Their strategy for blocking the apoptotic process would be to up-regulate Bcl production where this substance is responsible for apoptosis blockade. The prime of an immune response is to destroy free viruses and its cycle to stop its replication as this time of viruses is most vulnerable due to the encoding of antigenic protein. At the same time, viruses have developed methods to escape host's immunity but not destroying it at all because of its dependence on the hosts for survival and providing sites for creating new viruses for further infection to new hosts. Viruses achieve the evasion generally by 'encoding and expressing many different proteins to cause restriction, modification and redirection upon the cells of host's immune system'. ...read more.

Conclusion

Using HIV as an example, the virus derived proteins, embedded in the virus envelope interacts with the target host cell surface. The proteins that are inserted in the virus envelopes are the transmembrane subunit gp41, the gp120 surface subunit and they are glycoproteins. The gp120 guides the virion to attach to the lymphocytes' cell-surface receptors with the presence of CD4 protein on the lymphocytes membrane and interaction of gp120 and CD4 are induced. Besides, gp41 promotes the fusion of membrane of the viruses and host cells. The interaction between the two leads binding of gp120 with CD4. This causes a conformational change and brings about of gp120 binding with a second protein: The chemokine receptor 5, known as CCR-5. This further brings the HIV virus into close proximity with the host's membrane and the final stage is the fusion of the virus-cell membrane allowing virus to gain access into the host cell's cytoplasm. Vaccinations have been considered to be the possible solutions for persistence infections, however, it turns out to be 'low-level probability and high-level of uncertainty'. (Maurice R Hilleman, 2004) There are more successful developments on the prophylactic vaccines for the hit and run viruses than the hit and stay viruses for example the RNA viruses such as HIV or the hepatitis B virus. The alternative treatment for these infections can be treated by antiviral chemotherapeutic drugs which brings the viral load to the minimum and to retain hosts immune function for the least protection against pathogens. ...read more.

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