ANNUAL REVIEWS
Annu. Rev. Med. {991. 42:247-59
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Annu. Rev. Med. 1991.42:247-259. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
RESISTANCE OF VIRUSES TO
ANTIVIRAL DRUGSl
A. G. FreiJeld, M.D., and J. M. Ostrove, Ph.D.
Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 KEY WORDS:
herpes simp kx virus, varicella zoster virus, cytomegalovirus
ABSTRACT
In recent years, substantial advances in antiviral therapy have been made; however, in the immunocompromised host, antiviral drug resistance is becoming an issue of increasing clinical importance. Understanding the mechanism of action of antiviral agents, especially those used to treat herpesvirus infections, may enable us to design new therapeutic agents and better treatment regimens to deal with antiviral drug resistance. INTRODUCTION
Over the past 30 years, a number of antiviral agents have emerged from the laboratory and come into common clinical use. The widespread use of these agents has been attended by concerns about the development of antiviral drug resistance. Although such concerns have proven to be largely unfounded in the past, the current prolonged use of antivirals in patients with profound immune deficiency has altered the situation. Increasingly, we are encountering virus strains that are resistant to a variety of agents. Insights into the biochemical and molecular mechanisms of antiviral resist ance, as well as an appreciation of the clinical scope of the problem, are important in order to treat viral diseases in a manner that is both effective and yet least likely to foster further problems with drug resistance. I The
US
Government has the right to retain a nonexclusive, royalty-free license in and to
any copyright covering this paper.
247
248
FRElFELD & OSTROVE
MOLECULAR BASIS OF RESISTANCE
Annu. Rev. Med. 1991.42:247-259. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
A review of the features of virus life cycles illuminates the points at which
contemporary antiviral drugs can interfere with virus infection (Figure 1). The viral life cycle consists of a series of interactions between the virus and its host cell. Virus attachment to the cellular membrane is the first of these interactions. Usually it involves the binding of a virus-encoded
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Annu. Rev. Med. {991. 42:247-59
Further
Quick links to online content
Annu. Rev. Med. 1991.42:247-259. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
RESISTANCE OF VIRUSES TO
ANTIVIRAL DRUGSl
A. G. FreiJeld, M.D., and J. M. Ostrove, Ph.D.
Medical Virology Section, Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892 KEY WORDS:
herpes simp kx virus, varicella zoster virus, cytomegalovirus
ABSTRACT
In recent years, substantial advances in antiviral therapy have been made; however, in the immunocompromised host, antiviral drug resistance is becoming an issue of increasing clinical importance. Understanding the mechanism of action of antiviral agents, especially those used to treat herpesvirus infections, may enable us to design new therapeutic agents and better treatment regimens to deal with antiviral drug resistance. INTRODUCTION
Over the past 30 years, a number of antiviral agents have emerged from the laboratory and come into common clinical use. The widespread use of these agents has been attended by concerns about the development of antiviral drug resistance. Although such concerns have proven to be largely unfounded in the past, the current prolonged use of antivirals in patients with profound immune deficiency has altered the situation. Increasingly, we are encountering virus strains that are resistant to a variety of agents. Insights into the biochemical and molecular mechanisms of antiviral resist ance, as well as an appreciation of the clinical scope of the problem, are important in order to treat viral diseases in a manner that is both effective and yet least likely to foster further problems with drug resistance. I The
US
Government has the right to retain a nonexclusive, royalty-free license in and to
any copyright covering this paper.
247
248
FRElFELD & OSTROVE
MOLECULAR BASIS OF RESISTANCE
Annu. Rev. Med. 1991.42:247-259. Downloaded from www.annualreviews.org Access provided by University of California - San Francisco UCSF on 02/03/15. For personal use only.
A review of the features of virus life cycles illuminates the points at which
contemporary antiviral drugs can interfere with virus infection (Figure 1). The viral life cycle consists of a series of interactions between the virus and its host cell. Virus attachment to the cellular membrane is the first of these interactions. Usually it involves the binding of a virus-encoded
@
