Download Enveloped RNA viruses

General Virology (contin.)
CLASSIFICATION OF
VIRUSES
Virus classification according to
envelope
 1. Enveloped viruses:
 Enveloped DNA viruses, e.g. Herpes viruses
 Enveloped RNA viruses, e.g. Togaviruses
 2. Non-enveloped viruses:
 Non-enveloped DNA viruses, e.g. Adenoviruses
 Non-enveloped RNA viruses, e.g. Picornaviruses
 All RNA viruses are enveloped except: picornaviruses,
reoviruses and caliciviruses.
 All DNA viruses are enveloped except: Adenoviruses,
human papilloma viruses and parvoviruses.
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Virus classification according to the
genome
 1. DNA viruses:
 Enveloped-DNA viruses: e.g. Herpes viruses, Poxviruses
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and Hepadnaviruses.
Non-enveloped DNA viruses: e.g. Adenoviruses,
Parvoviruses, and Papillomaviruses.
2. RNA viruses:
Enveloped RNA viruses:e.g. Myxoviruses,
Rhabdoviruses, Togaviruses, Arboviruses, Retroviruses and
Coronaviruses
Non-enveloped RNA viruses: e.g. Reoviruses
Virus classification according to host
 1. Human: e.g.Varicella zoster.
 2. Arthropod: e.g.Yellow fever virus.
 3. Animal: e.g. Rabies virus.
 4. Plants: e.g.Tobacco mosaic virus
Virus classification according to
disease produced by the virus
 1. Respiratory viruses
 2. Enteric viruses
 3. Hepatitis viruses
VIRAL REPLICATION
 Viruses are metabolically inert, so they are
obligate intracellular parasites replicating only
inside living cells.
Virus Replication Cycle
 It can be divided into the following stages:
 1. Attachment
 2. Penetration
 3. Uncoating
 4. Transcription
 5. Translation
 6. Assembly
 7. Release
Virus growth cycle
 1. Attachment:
This is a specific interaction where the virus
attaches by viral surface proteins to specific
receptors on the host cell plasma membrane e.g.
human immunodeficiency virus attaches to CD4
receptors.
 2. Penetration: The entire virus (or sometimes only
the genome) enters the cell by two ways:
 Endocytosis: the cell membrane invaginates around the
adsorbed virus particle.
 Fusion may occur between the viral envelope and host cell
membrane releasing the naked nucleocapsid into the host cell
cytoplasm.
 3. Uncoating:
The protein coat of the virus is removed. This is
mainly carried out by host cell enzymes contained
in lysozymes.
 4. Transcription:
Production of virus mRNA occurs using the virus
genome as a template. In positive sense RNA viruses
the genome itself acts as mRNA.
 5. Translation:
Virus mRNA attaches to the host ribosomes and
directs the synthesis of virus-specific proteins. This
period of synthetic activity (synthesis of viral
nucleic acid and proteins) is called the eclipse
period because no viral particles are detected
inside the host cell.
 6. Assembly:
Newly synthesized nucleic acid molecules and
structural proteins assemble to form particles of the
new virus progeny.
 7. Release:
 The new particles are released from the cell by one
of two ways:
 Budding: a gradual process of extrusion through the cell
membrane. Viruses released by budding are enveloped
viruses.
 Rupture of the host cell (cytolysis): usually occurs in non
enveloped viruses.
ANTIVIRAL
CHEMOTHERAPY
Limitations
 Because viruses are obligate intracellular parasites, antiviral
agents must be capable of selectively inhibiting viral functions
without damaging the host.
 This makes the development of such drugs very difficult.
 Another limitation is that many rounds of virus replication
will have occurred during the incubation period and the virus
will have therefore spread before symptoms appear, making a
drug relatively ineffective.
Sites of action of major
antiviral drugs
The Mechanisms of Action of Antiviral
Drugs
I-Inhibition of Attachment and
Uncoating of the Virus
A. Fusion Inhibitor
 It blocks the virus and cellular membrane fusion step e.g. Fuzeon
used in human immunodeficiency virus (HIV) infection.
B. Inhibitors of Uncoating
 Amantadine and Rimantadine: specifically inhibit
influenza A viruses by blocking viral uncoating. They
must be administered prophylactically to have a
significant protective effect.
II- Inhibition of Nucleic Acid Synthesis
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A. Agents that inhibit polymerase
These are nucleoside-like molecules that inhibit DNA or
RNA polymerases.
Examples:
Acyclovir: It acts on virus encoded DNA polymerase. It
is effective against Herpes simplex virus (HSV) and
varicella-zoster virus (VZV).
It is only activated in viral infected cells because the
viral thymidine kinase is required to activate the drug
by placing the first phosphate on the drug.
Ganciclovir: A derivative of acyclovir and it is effective
in infections caused by Cytomegalovirus (CMV).
B. Reverse Transcriptase Inhibitors
i.Nucleoside analogues
 Examples:
 1- Azidothymidine (AZT): It inhibits HIV replication by
blocking synthesis of proviral DNA.
 2-Dideoxyinosine (DDI): It also inhibits HIV as AZT, but it is
less toxic.
 3- Lamivudine: Used in treatment of HIV and HBV infections.
ii.Non-nucleoside analogues
 They act by binding directly to reverse transcriptase (RT).
 Nevirapine: effective against HIV.
C. Drugs interfering with mRNA synthesis
 Ribavirin: Effective against DNA and RNA viruses. It is
used in treatment of HCV and respiratory syncytial virus
(RSV).
D. Interferons
 Synthetic interferons are now available and are prepared by
recombinant technology (e.g. alpha interferon used in
chronic hepatitis C).
III- Inhibition of Cleavage of Precursor Polypeptides
 Such drugs inhibit the viral protease that is required at the
late stage of the replicative cycle to form the mature virion.
 Inhibition of the protease yields noninfectious viral particles
e.g. saquinavir and indinavir which inhibit proteases
encoded by HIV.
IV- Inhibition of Release of Virus
Neuraminidase Inhibitors
 These drugs are effective against both influenza A & B
viruses.
 They act by inhibiting the release of virus from infected cells.
This limits the infection by reducing the spread of the virus
from one cell to another.
 Two drugs are available which are given either by inhalation
or orally (Oseltamivir & Zanamavir).
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