Cell Bio- Viruses

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Characterization of viruses: (6)

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1. Viruses are small nucleoprotein particles which have capability to infect cell (host cell) and to reproduce in it.
2. Viruses exert high level of specificity as to the type of cells which they infect.
3. They are intracellular parasites and their reproduction completely depends on host cell.
4. Their reproduction is mostly harmful to cell.
5. Viruses do not have a character of cellular organisms (noncellular organisms).
6. They do not have their own metabolism but they have their own genome and have capability to reproduce.

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Genophores of viruses can be:

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DNA as well as RNA

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Virus particles is refereed to as:

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Virion

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Basic structure of the virion:

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1. Nucleic acid (Genophore)
2. Capsid
3. Outer envelope (only in enveloped viruses)

4. Nucleocapsid: capsid with nucleic acid inside

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Morphology of virions:

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Virions have various shapes.
1. Bacterial viruses (bacteriophages)
2. DNA viruses of eukaryotic cells
3. RNA viruses of eukaryotic cells

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Size of virions:

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20- 400 nanometers

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Viral nucleic acid
a) DNA viruses
b) RNA viruses

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a)
1. Single- stranded linear DNA
2. Single- stranded circular DNA
3. Double- stranded linear DNA
4. Double- stranded circular DNA
b)
1. Single- stranded RNA (+ssRNA, -ssRNA)
2. Double stranded RNA

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Size of viral nucleic acid:

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3000- 300 000 nucleotides

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Viral nucleic acid forms:

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Viral genom

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Nonfragmented viral genom:

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1 genophore

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Fragmented viral genom:

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More fragments, i.e. more genophores

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Coding sequence/ regions of the genome:

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Cistronic/ structural genes:

Structural genes encode proteins of capsid and also other proteins which have often enzymatic activity and which are involved in virus reproduction (DNA polymerases, RNA polymerases)

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Overlapping genes:

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In some viruses, coding sequences are partly overlapping

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Promotores:

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Regulatory sequences/ regions of the genome

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Size of viral genome:

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3- 150 genes

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Mutations of viral genome: (2)

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1. Mutations occur with high frequency (mostly there are no repair mechanisms)
From the point of view of medicine, mutations of viruses are highly important.

2. Attenuated virus: mutated viruses with unchanged antigenic properties but with reduced pathogenicity (vaccines)

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Recombination of viral genome: (2)

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1. The recombination of viral genome occurs when a cell is simultaneously infected by two similar viruses.

2. High frequency of recombination occurs in viruses with fragmented genome.
From the point of view of medicine, recombinations of viruses are again highly important.

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Capsid:

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Protein container in which viral nucleic acid (genophore/ genophores) is enclosed.

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Structure of capsid:

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1. Made of subunits (capsomers)
2. Capsomers are mostly identical and they are made of one or, in some cases, several proteins.
3. Capsid represents quaternary structure formed by capsomers

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Morphology of capsid: (4)

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1. Capsid can be various in shape
2. Regular polyhedron made of 20 triangular faces and 12 vertices (icosahdron) (spherical viruses)
3. Helical cylinder (rod- shaped viruses)
4. Specific shape of bacterieophages (head, tail with filaments)

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Outer envelope: (3)

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1. Some viruses (enveloped viruses) are, in addition, enveloped by outer membrane made of lipid bilayer (outer envelope)
2. Outer envelope is derived from plasma membrane of host cell. However, proteins of outer envelope are viral, i.e. they are coded by viral genes.
3. Proteins (often glycoproteins) of outer envelope participate in specific interactions of virus particle with host cell.

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Reproduction of viruses
- There are two possibilities after the penetration of virion into cell:

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1. Virus is multiplied within the cell and virions are released form the cell. This is often accompanied with cell disintegration. Mentioned process is refereed to as reproductive (lytic cycle)

2. Viral genome is incorporated into the genome of host cell and thus viral genome is replicated together with the genome of host cell. This phenomenon is known as virogeny (lysogeny in the case of bacterieophages)

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Strategy of the replication of viral genome accompanying the reproduction of virus depends on the type of nucleic acid incorporated into virion:

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1. dsDNA viruses: according to usual scheme
2. ssDNA viruses:
+ssDNA--> ssDNA (--> transcription & translation)--> +ssDNA
3. dsRNA viruses:
+RNA/-RNA--> -RNA/+RNA (--> translation)
RNA dependent RNA polymerase (RNA replicase) is required, virus must carry the gene for RNA replicase or virus must bring ready RNA replicase in nucleocapsid

4. +ssRNA viruses:
+ssRNA--> -ssRNA--> +ssRNA (--> translation)
5. -ssRNA viruses:
-ssRNA--> +ssRNA (-->translation) --> -ssRNA
6. RNA viruses with reverse transcriptase:
+ssRNA--> +RNA/-DNA--> +DNA/-DNA (incorporation into the genome of host cell)--> +ssRNA (--> translation)
RNA dependent DNA polymerase (reverse transcriptase) is required, virus brings ready reverse transcriptase in nucleocapsid.
7. DNA viruses with reverse transcriptase:
+DNA/-DNA--> +ssRNA (--> translation)--> +RNA/-DNA ---> + DNA/-DNA

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Reproductive (lytic cycle)
Viral reproductive cycle is accomplished in three stages:

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1. Adsorption of virion on cell surface and its penetration into cell
2. Reproduction of virion within the cell
3. Release of virions from the cell

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Adsoption of virion on cell surface and its penetration: (First stage of viral reproductive cycle)
a) What?
b) Mechanism of virion penetration into the cell

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a) Adsorption of virion on cell surface depends on the presence of specific receptors on the surface of host cell

b) 1. Fusion of outer envelope with plasma membrane (release of nucleocapsid into cytoplasm)
2. Receptor mediated endocytosis
3. Bacterieophages inject their nucleic acid into cytoplasm

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Reproduction of virion within the cell: (Second stage of the viral reproductive cycle) (lytic cycle)

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1. Release of nucleic acid from capsid inside of the cell. Host cell further carries out the reproduction/ multiplication of virion.

2. Synthesis of viral nucleic acid, proteins of capsid and proteins of outer envelope are independently accomplished in various compartments of the cell.

3. Maturation of virions: assembly of individual components to form virion structure is an auto-aggregation process.
- Early proteins
- Late proteins

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Release of virions from the cell: (Third stage of viral reproductive/ lytic cycle)

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1. Lysis of the cell: lytic enzymes of the virus (bacterieophages), autolytic processes of damaged host cells

2. Exocytosis of virions: active process (budding) where outer envelope of virion is formed from plasma membrane of host cell

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Virogeny and lysogeny (second form of reproduction of viruses):

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Viral DNA is replicated within host cell but virions are not formed and released. Viral DNA is:
1. Replicated within host cell but virions are not formed and released
2. Incorporated into a chromosome of host cell and is replicated together with the chromosome. Such viral DNA is refereed to as provirus

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In the case of bacterieophages, virogeny is known as:

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Lysogeny

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Provirus can be induced to start:

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Lytic cycle or (lysogenic cycle in bacterieophages)

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Horizontal transmission:

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Direct transmission of virus from one host to another host

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Vertical transmission:

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Transmission of virus from parental generation to offspring

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Transmission of virus from host to host via:

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Vectors (e.g. insect)

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Interaction virus- cell:

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1. Death of the cell:
Degenerative process within the cell or active lysis of the cell by lytic enzymes of the virus

2. Cytopathic effect:
Damage of any function of the cell (--> damage of tissue/organ function), damage can be reversible

3. Without cell damage:
Virus is reproduced within the cell but it does not damage the cell

4. Slow viruses:
They do not damage the cell but they change some characteristics of the cell

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Classification of viruses according to the type of host cell:

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1. Bacterial viruses (bacteriophages)
2. Eukaryotic viruses

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Eukaryotic viruses:

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1. Viruses of fungi
2. Plant viruses (tobacco mosaic virus, plum pox virus)
3. Animal viruses

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Classification of viruses according to the type of their genome:

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1. dsDNA viruses
2. ssDNA viruses
3. dsRNA viruses
4. +ssRBA viruses
5. -ssRNA viruses
6. RNA viruses with reverse transcriptase
7. DNA viruses with reverse transcriptase

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Animal dsDNA viruses:

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1. Papovaviruses (circular dsDNA)
2. Adenoviruses (linear dsDNA)
3. Herpesviruses (linear dsDNA)
4. Poxviruses (linear dsDNA)

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Papovaviruses:

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Papillomaviruses (formation of warts, 90% of human population are infected)

Polyomavirus: virus SV40 (simian virus)

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Adenoviruses:

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Respiratory, GI and ophthalmic infections

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Herpesviruses:

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1. Herpes simplex 1 virus (herpes/herpes simplex, 90% of human population infected)
2. Varicella- zoster virus (chickenpox/varicella, shingles/herpes zoster)
3. Virus EBV (Epstein- Barr virus) (infectious mononucleosis, Burkitt`s lymphoma)

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Papoviruses:

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Smallpox virus (smallpox/ variola)

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Animal ssDNA viruses:

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Parvoviruses (fifth disease/ erytherma infectiosum

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Animal dsRNA viruses:

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Reoviruses (mostly asymptomatic respiratory and GIT infections)

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Animal +ssRNA viruses: 2

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1. Picornaviruses
2. Togaviruses

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Picornaviruses:

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1. Poliovirus (infantile paralysis/ polopmyelitis)
2. Hepatitis A virus (HAV)
3. Rhinovirus (common cold/ rhinitis)

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Togaviruses:

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1. Encephalitis virus (tick- borne virus)
2. Rubella virus (German measles/rubella)

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Animal -ssRNA viruses: (4)

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1. Orthomyxoviruses (segmented RNA)
2. Paramyxoviruses (nonsegmented RNA)
3. Rhabdoviruses (nonsegmented RNA)
4. Filoviruses (nonsegmented RNA)

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Orthomyxoviruses:

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1. Influenza virus A (flu/influenza in man, birds and pig)
2. Influenza virus B (flu only in man)

The source of new strains of flu is a rearrangement of genomic segments (--> epidemics of flu)

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Paramyxoviruses:

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Measles virus (mesles/morbilli)

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Rhabdoviruses:

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Rabies virus (rabies)

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Filoviruses:

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Ebola virus (Ebola virus disease)

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Animal RNA viruses with reverse transcriptase:

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Retroviruses:
- Virus HIV-1 (human immunodeficiency virus) (AIDS= acquired immune deficiency syndrome)
- Virus HTLV-1 (human T-cell lymphotropic virus) (T lymphoma, oncogenic retroviruses of animals (Rous sarcoma virus))

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Animal DNA viruses with reverse transcriptase:

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Hepadnaviruses:
- Hepatitis B virus (HBV) (liver inflammation/ hepatitis)

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Oncogenic viruses
a) What?
b) Which?

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a)
Viruses which can cause tumor transformations
b)
1. RNA oncogenic viruses
2. DNA oncogenic viruses

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RNA oncogenic viruses:

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Retroviruses:
- Retroviruses containing an oncogene in their genome (Rous sarcoma virus)
- Retroviruses which do not contain an oncogene in their genome (HTLV-1)

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DNA oncogenic viruses: 4

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1. Papovaviruses:
- papillomaviruses (human papillomavirus)
- polymaviruses (SV 40)
2. Adenoviruses
3. Herpesviruses (EBV)
4. Hepadnaviruses (hepatitis B virus)