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Basic virology (a.3)
1. BASIC MEDICAL VIROLOGY
Ludhang Pradipta Rizki MD., M.Biotech, Clinical Microbiologist
Departement of Microbiology Faculty of Medicine UGM
2. BASIC MEDICAL VIROLOGY
Virology is the bioscience for study of
viral nature and the relationship
between viruses and hosts.
Viruses often cause serious diseases,
relate to some cancers and
congenital deformities, also can be
used as tool for genetic engineering.
Concepts
4. The General Structure of Viruses
Viruses not living organisms
Basic Properties
Cannot replicate independently
Cannot survive long-term independently
Contain no ribosomes (cannot synthesise protein)
6. Size and Structure
Viruses are much smaller (φ 20-300nm) than
bacteria, fungi and protozoa
Basic Properties
Viruses structure is simple
Nucleocapsid
Protein shell (capsid)
Many viruses also have an outer envelope
Methods of Analysis use Electron microscopy
(the resolution is 5 nm) and X-ray crystallography
11. Structure and Composition
The Virus particle called a virion
Structure
Virion consists of nucleocapsid with 2 components
(the single or double stranded, linear, circular or
segmented DNA or RNA genome)
Virion with surrounding protein shell called the
capsid
12. Capsid
The capsid`s repeating protein units form structural
units (Capsomeres)
Structure
Capsomers arranged with either helical or
isocohedral symmetry, complex symmetrty
Nucleocapsid of some human viruses is “naked”
17. Composition of Viruses
Viral Nucleic Acids
Structure
Viral Protein and Viral enzymes
Viral envelopes
Viral core
Viral core :
The viral nucleic acid genome, in the
center of the virion, Control the viral
heredity and variation, responsible for
the infectivity
19. Viral Envelopes
Viral envelopes are lipoprotein and composed of an
inner structural derived protein and an outer host
cell derived lipid layer
Structure
It is acquired during viral maturation by a budding
process through a cellular membrane, viruses-
encoded glycoproteins are exposed on the surface
of the envelope
20. Viral Envelopes
In addition there are often projecting spikes of
glycoprotein (Viral Attachment Proteins (VAPs) to
host cells)
Structure
Not all viruses have the envelope, and viruses can
be divided into 2 kinds: enveloped virus and naked
virus
24. Atypical viral-like agents Structure
Defective viruses
Pseudovirions
Defective viruses (Hepatitis D) have viral protein but
defective nucleic acid (by mutation or deletion)
Cannot replicate without a helpervirus (Hepatitis B)
• Viral DNA replaced by host-cell DNA which has
fragmanted and been incorporated into the viral capsid
• Can infect but of course cannot replicate
25. Atypical viral-like agents Structure
Viroids
Prions
Only single small molecule of RNA (subviral particles)
No capsid or envelope
How they replicate is unclear
Can infect plants but not humans
Prions a single glycoprotein with no detectable nucleic acid,
yet replicate.
The protein is encoded by a host cell gene, not viral gene
The increase in numbers of prions infected in human
nervous tissue (Cruetzfeldt-Jakob disease)
26. The Host Cell
Abortive (no replication, no visible host cell
effect, no disease)
Cytolytic (cell death and virus dissemination
then disease, then death or recovery of the host)
Persistent
Three major types of viral infection occurs:
Latent
No effect on the cell, but may re-activate (e.g.herpes)
Productive
Give chronic carriage or disease (e.g. hepatitis B)
Transforming
Producing tumours (e.g. EBV lymphomas)
32. Baltimore Clasisification Genome
The Baltimore classification based on the relationship of the
viral genome to its mRNA and recognizes 7 classes of viruses
39. Viruses Replication Replication
Early stage of recognation, attachment, penetration
and uncoating
a. Recognation and attachment are due to interaction
between each type of virus and specific receptor on
the human cell.
b. Penetration or entry is either by uptake into
phagosome or by fusion of viral and host cell
membranes
c. Uncoating in the cell cytoplasm is by cell enzymes
from lysosomes, which remove the virus protein coat
and so make the viral genome accessible for the
next stage
41. Viruses Replication Replication
Central stage of mRNA synthesis, protein
synthesis and genome replication
1. mRNA synthesis
2. Early protein synthesis
3. Genome replication
4. Late protein synthesis
42. Viruses Replication Replication
a. mRNA synthesis by transcription
The method of transcription to form depand on the genome,
arranged by Baltimore classification (6 groups)
Unnecessary for positive sense single strand RNA Viruses,
where they definition their RNA is mRNA
b. Early protein synthesis
By translation of the above mRNA using host cell ribosomes in
the citoplasm to make viral protein
If the viral genome is a single nucleic acid molecule, one large
polyprotein is produced and the claved by enzymes into a
number of smaller proteins
If the viral genome consist several mRNAs are made, each
translated into one protein
These early protein are usually enzymes and regulatory
molecules for the next stage
43. Viruses Replication Replication
c. Genome replication
Like mRNA synthesis depend on type of genome
d. Late protein synthesis
Late protein synthesis of viral mRNA produces the
capsid structural protein
44. Viruses Replication Replication
Final stage of assembly and release
(with or without envelopment)
Assembly of progeny virus particles
Release of unenveloped virus
Enveloped viruses
45. Viruses Replication Replication
Final stage of assembly and release (with or without
envelopment)
1. Assembly of progeny virus particles
Occurs in the cytoplasm
Occurs in the nucleus (herpes, adeno, papilloma viruses)
Occurs at the cell membrane of the host cell
The viral genome is assembled with the capsid proteins
and the viral enzymes into new viral progeny
2. Release of unenveloped virus
Occurs in thought the host cell wall by rupture (“lysis”)
Causing cell death
46. Viruses Replication Replication
Final stage of assembly and release (with or without
envelopment)
3. Enveloped viruses
Incorporating host cell nuclear or plasma membrane
components
Inserted viral proteins and glycoproteins to form the
envelope prior to release
Realese is usually by budding, and does not necessarily
cause cell death
Infectious enveloped virus can be shed for a long time
48. Viral Genetic
A. Mutations
The RNA or DNA (“wild type”) of virus may mutate by 2 mechanisms:
Mutations by base subtitutions
One base of another by mistake or by mutagen (physical or c
hemical). This mutations called a missense mutation if a different
amino acids is code. This mutations called a nonsense mutation if no
amino acids is code,stopping protein synthesis, and thus usually a
lethal mutations
Frameshift
When one or more base pairs are deleted or added
Thus shifting the reading frame and leading to the wrong amino acids
Hence an inactive protein
50. Viral Genetic
B. Interaction (Genetic exchanges)
Four major interaction can occur between host and virus,
or 2 viruses infecting the same cell
Recombination
Reassortment
Complementation
Phenotypic mixing
Viruses were originally distinguished from other infectious agents because they are
especially small (filterable) and because they are obligatory intracellular parasites.
Virtually all cervical and anal cancers are caused by
human papillomavirus (HPV). A vaccine against four HPVs is
recommended for 11- to 12-year-old girls and boys.
Epstein-Barr (EB) virus was isolated from Burkitt’s lymphoma
Cells.
The question of whether viruses are living organisms has an ambiguous answer. Life can be defined as a complex set of processes
resulting from the actions of proteins specified by nucleic acids. The nucleic acids of living cells are in action all the time.
Because viruses are inert outside living host cells, in this sense they aren’t considered to be living organisms.
Viruses have few or no enzymes of their own for metabolism;
for example, they lack enzymes for protein synthesis and
ATP generation. To multiply, viruses must take over the metabolic
machinery of the host cell.
Viral sizes are determined with the aid of electron microscopy.
Different viruses vary considerably in size. Although most are
quite a bit smaller than bacteria, some of the larger viruses (such
as the vaccinia virus) are about the same size as some very small
bacteria (such as the mycoplasmas, rickettsias, and chlamydias).
Viruses range from 20 to 1000 nm in length.
The comparative sizes of several viruses and bacteria are shown in
A virion is a complete, fully developed, infectious viral particle
composed of nucleic acid and surrounded by a protein coat outside
a host cell. Viruses are classified by their nucleic acid and
by differences in the structures of their coats
The nucleic acid of a virus is protected by a protein coat called
the capsid . The structure of the capsid is ultimately
determined by the viral nucleic acid and accounts for
most of the mass of a virus, especially of small ones. Each capsid
is composed of protein subunits called capsomeres.
In contrast to prokaryotic and eukaryotic cells, in which DNA is always the primary genetic material (and RNA plays
an auxiliary role), a virus can have either DNA or RNA—but never both. The nucleic acid of a virus can be single-stranded
or double-stranded. Thus, there are viruses with the familiar double-stranded DNA, with single-stranded DNA, with doublestranded
RNA, and with single-stranded RNA. Depending on the virus, the nucleic acid can be linear or circular
Just as we need taxonomic categories of plants, animals, and bacteria,
we need viral taxonomy to help us organize and understand
newly discovered organisms. The oldest classification of viruses
is based on symptomatology, such as for diseases that affect the
respiratory system. This system was convenient but not scientifically
acceptable because the same virus may cause more than one
disease, depending on the tissue affected.
In addition, this system
artificially grouped viruses that don’t infect humans. viral species
is a group of viruses sharing the same genetic
information and ecological niche (host range). Specific epithets
for viruses aren’t used. Thus, viral species are designated by
descriptive common names, such as human immunodeficiency
virus (HIV), with subspecies (if any) designated by a number
(HIV-1)
Traditionally viruses have been
classified phenotypically, by
appearance, by size, by genome type,
by replication strategy, by host, and by
diseases caused. There are two main
classification systems in use – the
International Committee on Taxonomy
of Viruses (ICTV) classification and
the Baltimore classification system.
The Baltimore classification divides
viruses into seven groups based on a
combination of genome type and
replication strategy, specifically how
mRNA is formed from the original
genome.
Following attachment, entry, and uncoating, the viral DNA is released into the nucleus of the host cell.
Transcription of a portion of the viral DNA—the “early”
genes—occurs next. Translation follows. The products of
these genes are enzymes that are required for the
multiplication of viral DNA. In most DNA viruses, early
transcription is carried out with the host’s transcriptase
(RNA polymerase); poxviruses, however, contain their own
transcriptase.
3. Sometime after the initiation of DNA replication, transcription
and translation of the remaining “late” viral genes
occur. Late proteins include capsid and other structural
proteins.
4. This leads to the synthesis of capsid proteins, which occurs
in the cytoplasm of the host cell.
5. After the capsid proteins migrate into the nucleus of the
host cell, maturation occurs; the viral DNA and capsid
proteins assemble to form complete viruses. Complete viruses are then released from the host cell.
Pathways of multiplication used by various RNA-containing viruses. (a) After
uncoating, single-stranded RNA (ssRNA) viruses with a + strand genome are able
to synthesize proteins directly from their + strand. Using the + strand as a
template, they transcribe − strands to produce additional + strands to serve as
mRNA and be incorporated into capsid proteins as the viral genome. (b) The
ssRNA viruses with a − strand genome must transcribe a + strand to serve as
mRNA before they begin synthesizing proteins. The mRNA transcribes
additional − strands for incorporation into capsid protein. Both ssRNA and
(c) dsRNA viruses must use mRNA (+ strand) to code for proteins,
including capsid proteins.
Model for antigenic shift in influenza virus. If a pig were
infected with a human influenza virus and an avian
influenza virus at the same time, the viruses could
reassort and produce a new virus that had most of the
genes from the human virus but a hemagglutinin and/
or neuraminidase from the avian virus. The resulting
new virus might then be able to infect humans and
spread from person to person, but it would have surface
proteins (hemagglutinin and/or neuraminidase) not
previously seen in influenza viruses that infect humans.
