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Afiono Agung Prasetyo

http://afie.staff.uns.ac.id/

BASIC VIROLOGY

Ubiquitous
Some viruses cause disease
Some viruses are useful

Why Important?

A very small, non-cellular parasite of cells. Its genome


(DNA/RNA), is enclosed in a protein coat (capsid)
Are viruses living or nonliving?
Viruses should not be confused with virus particles or
virions
Virions are not cells
They do not contain organelles, except
arenaviruses
Viruses do not replicate or self-replicate themselves, but
are being replicated

The nature of viruses

Virus isolate: any particular virus culture, an instance of


a given virus.
A viral strain: a biological variant of a virus that is
recognizable because it possesses some unique
phenotypic properties that remain stable under natural
conditions.
Serotypes: Strains that possess unique-stable antigenic
properties

Isolate Strain - Serotype

the virus-first hypothesis


the reduction hypothesis
the escape hypothesis
???

OLD HYPOTHESES TO EXPLAIN


THE ORIGIN OF VIRUSES

Taxa: written in italics


Please check:
http://www.phene.cpmc.columbia.edu/index.htm
http://www.danforthcenter.org/iltab/ictvnet/
Virus species are man-made taxonomic classes and
do not have hosts, vectors, or sequences.

SPECIES NAMES AND


HOW TO WRITE THEM

Capsid
+ internal membrane?
+ envelope?
+ virus RNA in DNA viruses?
+ cell molecules?

DNA: ss linear, ds RNA, ss circular, ds circular


RNA: ss linear, ds linear, ss circular

Genome:

VIRION COMPONENTS

Picornaviridae
Caliciviridae
Astroviridae
Togaviridae
Flaviviridae
Coronaviridae
Ateriviridae
Arteriviridae
Rhabdoviridae
Filoviridae
Paramyxoviridae
Orthomyxoviridae
Bunyaviridae

Arenaviridae
Bornaviridae
Reoviridae
Retroviridae
Polyomaviridae
Papillomaviridae
Adenoviridae
Parvoviridae
Herpesviridae
Poxviridae
Hepadnaviridae
Unclassified Agents

IMPORTANT FAMILIES

Afiono Agung Prasetyo


http://afie.staff.uns.ac.id/

VIRUS REPLICATION &


PATHOGENESIS

Entry
Barriers?
Virus receptors & attachment factors?
Spread
Replication
Shedding

The Sequential Steps In Viral Infection

Attachment
Entry & Uncoating
Genome replication + protein production
Replication sites?
Intracellular trafficking?
Assembly
Release
>>> See Baltimore classification

The Sequential Steps of Viral


Replication

Productive viral replication may not destroy host cells


& is not required for cytopathology
Cellular responses to viruses
Hijack the cell
The virus is being replicated by the cellular
machines
Virus may induce cell death (apoptosis &/ necrosis)

How Do Viruses Affect Cells?

Infection
Acute
Chronic
Productive
Abortive
Latent
re-initiating / reactivation
Permissive cells
Tropism

CONCEPTS

Disease
Virulence
Invasiveness
Essential genes, virulence genes, and virulence
determinants
Inflammatory responses to viral infection
Fate of the infected cell, tissue, and host
Cytopathicity and cell death

CONCEPTS

Age as a determinant of susceptibility to viral infection


Clearance of virus infection and chronic viral infection
A necessary evil: tissue damage occurs during beneficial
immune responses
Antibody-enhanced diseases
Virus-induced autoimmunity
Virus-induced immunosuppression
Mutation and selection of viral variants
Quasi species

CONCEPTS

Oncogenic viruses
Virus-induced transformation
The transformed cellular phenotype
Viral transduction of an oncogene
Activation of the transforming potential of oncogenes
Oncogene activation
Transformation by molecular mimicry and insertional
mutagenesis
Oncogenesis mediated by essential viral proteins

CELL TRANSFORMATION BY VIRUSES

Sensing viral infections


IFN, IL, TNF
Monocytic cells, Dendritic cells, Natural Killer cells
Actions of innate responses on downstream adaptive
responses
Viral strategies for counteracting or taking advantage
of cytokine action?

INNATE RESPONSES
TO VIRAL INFECTIONS

Induction of adaptive immune responses


Viral antigen recognition
Cytokines and chemokines
Antiviral activities of antibody in vitro & in vivo
Adaptive immune memory
Viral strategies to evade the adaptive immune
response?

ADAPTIVE IMMUNE RESPONSE


TO VIRUSES

Afiono Agung Prasetyo


http://afie.staff.uns.ac.id/

DIAGNOSTIC VIROLOGY

Important variables?
The best specimens for the diagnosis of acute viral
infections?
Viral culture?
Immunological assays?
Molecular assays?
The significant of viral detection?

SPECIMENS FOR VIRAL DIAGNOSIS

Epidemiology, diagnostics, forensic studies,


phylogeography, origin, evolution, and taxonomy
First question to be answered during an outbreak of
a virus epidemic concern is the virus identity and
origin
Determining the relationship of a newly identified
virus with all other previously characterized and
sequenced viruses.
Virushost association

Applications Of Phylogeny In Virology

Afiono Agung Prasetyo


http://afie.staff.uns.ac.id/

ANTIVIRAL AGENTS

Medical value
Drug selectivity, resistance, and drug targets
General aspects of antiviral drug targets
Factors affecting the development of drug resistance

OVERVIEW

Targeting drugs to specific stages of virus infection


Inhibition of viral attachment and entry: Enfuvirtide
(T-20), CCR5 blockers
Inhibition of viral uncoating: Adamantane derivatives
Inhibition of viral genome replication: nucleoside
analogues, non-nucleoside inhibitors (Foscarnet &
NNRTIs), integrase inhibitors
Inhibition of viral assembly and maturation: Protease
inhibitors, Neuraminidase inhibitors

MECHANISMS OF SPECIFIC
ANTIVIRAL DRUGS

Viral dynamics and the role of the immune system in


antiviral therapy
Interplay between anti-human immunodeficiency
virus therapy, viral dynamics, and the immune
system
Compartments and reservoirs
Drug resistance
Clinical impact
Strategies to combat drug resistance

Principles of Antiviral Therapy