Persistent Viral Infections Istvan Boldogh Thomas Albrecht



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Persistent Viral Infections

Istvan Boldogh

Thomas Albrecht

David D. Porter

General Concepts

Definition

Persistent infections are characterized as those in which the virus is not cleared but remains in specific cells of infected individuals. Persistent infections may involve stages of both silent and productive infection without rapidly killing or even producing excessive damage of the host cells. There are three types of overlapping persistent virus-host interaction that may be defined as latent, chronic and slow infection.



Pathogenesis

The mechanisms by which persistent infections are maintained involve both



Reactivation of a latent infection may be triggered by various stimuli, including

  • changes in cell physiology,

  • superinfection by another virus, and

  • physical stress or trauma.

Host immunosuppression is often associated with reactivation of a number of persistent virus infections.

Persistent Infections by Organ System

Some viruses can establish persistent infection at the same time in different cell types of one or more tissues or organs. For example, the primary site for latency of cytomegalovirus is thought to be peripheral blood monocytes, but the virus may induce disease and can be detected in cells of several organs (e.g., kidney, lung, and those of the digestive or central nervous system). Table-1 categorizes selected human viruses by organ systems in which the virus is believed to be primarily persistent.



In Vitro Models of Persistence

Three kinds of persistent infection can be maintained in cell cultures:

  • chronic focal,

  • chronic diffuse, and

  • latent.

These infections may model key aspects of persistent infections in vivo.

Control

No measures to eradicate persistent viruses have been developed. Vaccination, interferon and antiviral drugs can reduce the frequency of clinical recurrence and ameliorate clinical symptom, yet the virus continues to remain associated with the host.





INTRODUCTION

Medical science has begun to control a number of acute virus infections, many by drug treatment and/or immunization, but persistent virus infections are largely uncontrolled.



Diseases caused by persistent virus infections include

  • acquired immune deficiency syndrome (AIDS), AIDS-related complexes,

  • chronic hepatitis,

  • subacute sclerosing panencephalitis (chronic measles encephalitis),

  • chronic papovavirus encephalitis (progressive multifocal leukoencephalopathy),

  • spongioform encephalopathies (caused by prions),

  • several herpesvirus-induced diseases, and

  • some neoplasias.

The pathogenic mechanisms by which these viruses cause disease include disorders of biochemical, cellular, immune, and physiologic processes. Ongoing studies are rapidly advancing our understanding of many persistent infections. Viruses have evolved a wide variety of strategies by which they maintain long-term infection of populations (see Ch. 48), individuals, and tissue cultures. This chapter primarily describes persistent infections in vivo and focuses on viruses that persist in humans.

Classification

Persistent infections are those in which the virus is not cleared from the host following primary infection, but remains associated with specific cells. Figure 46-1 presents a classification scheme of the principal types of persistent infections in vivo.




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