viruses and prions

Viruses and Prions

1

مايكرو نظري/ ثالث اسنان كركوك

د.زبيدة
22/10/2017
17

Introduction to Virology

Viruses are one of the smallest forms of microorganism and infect most other forms of life: animals, plants and bacteria.

They can also cause severe acute oral and orofacial disease, produce oral signs of systemic infection, and be transmitted to patients and dental staff.
2

The main features that characterize viruses

Small size (10–100 nm), averaging about one-tenth the size of a bacterium.
• genome consisting of either DNA or RNA but never Both.

single- (ss) or double-stranded (ds); linear or circular


3

The main features that characterize viruses

• metabolic inert outside the cells of susceptible hosts; viruses lack ribosomes – the protein-synthesizing

apparatus (viruses can only multiply inside living cells, i.e. they are obligate intracellular parasites).

4

Structure

Viruses consist of
1- a nucleic acid core containing the viral genome
2- surrounded by a protein shell called a capsid

3-The entire structure is referred to as nucleocapsid.

4-This may be ‘naked’, or it may be ‘enveloped’ within a lipoprotein sheath derived from the host cell membrane.

In many viruses (e.g. orthomyxo viruses, paramyxo viruses),

the ensheathment begins by a budding process at the plasma membrane of the host cell,
while others, such as herpes viruses, ensheath at the membrane of the nucleus or endoplasmic reticulum.






5

Nucleic acid :-

DNA or RNA
Single or double strand
Linear or circular
Intact or fragmented
Encodes very few proteins

The DNA viruses all have genome composed of Single molecule or genom.

Where as the genome of many RNA viruses consist of several different molecules or segments

6

proteins

Structural Capsid made of capsomeres
Made up of two or three different poly peptid chains
Offer protective sheath for Nucleic acid
Serves as antigens elicit an immune response
Some of protein have a special affinity for receptors on the surface of susceptable cell
Some of these protein have enzymatic activity
E.g. Human Immuno deficiency virus (HIV) contain revers transcriptase .
Where as several enzyme Neuraminidase , Lysozyme) are found in larger and more complex


7

Envelope

Some of virus enveloped themselves in a modified form of one of the cell membranes either
the outer membrane surrounding an infected host cell or internal membrane such as the nuclear membrane or endoplasmic reticulum.
Thus gaining an outer lipid bilayer Known as Viral Envelope
The lipid membrane itself and any carbohydrates present originate entirely from the host.

8

Viral lipid and carbohydrate

About 50–60% of the lipids are phospholipids; most of the remainder is cholesterol.
9

Virus symmetry 3 Types

1- Icosahedral symmetry :- (Isometric or Cuboidal)
Most animal viruses are Icoshydral or near spherical shape.
Capsomers consist of 5capsomers are called Pentons
Capsomers consist of 6capsomers are called hexon





10






11




12

Virus symmetry

2- Helical symmetry:- (Tubulare)
cosist of single type of capsomere surround the viral nucleic acid in the form of a helix or spiral to form a tubular nucleocapsid.
Most mammalian RNA viruses have this symmetry, where the nucleocapsid is arranged in the form of a coil and enclosed within a lipoprotein envelope.
13





14






15

3- Complex symmetry:-

These viruses possess a capsid that is neither purely helical nor purely Icosahedral . It may possess extra structure such as Protein tails
e.g. Enterobactriophage
Virus symmetry


16

Taxonomy

Historically based on :--
Host preference : plant, insect, animal, human
Target organ : respiratory, hepatic, entericVector :-arbovirus
Currently based on Molecular biology of genome and biophysical structure


17

Toxonomy

Viruses with simillar structural genomic & replication properties are grouped into
Families (Suffix viridae) e.g. Herpes viridae

Families subdivided into Genera (Suffix : virus) e.g. Herpes simplex virus, Cytomegalovirus , Viaricella zoster virus

Sub type based on nucleotide sequence and Genetic reacttivities e.g. Herpes simplex virus type 1 , Herpes simplex virus type 2
18

Toxonomy

Nucleic acid DNA RNA
Envelope Yes No
Symmetry Cubic Helical
(Icosahedral) (Cylindrical)
complex
19

DNA Viruses

Enveloped DNA virus
1- Parvo virus
2- Herpes virus
3- Pox virus


Non enveloped DNA virus
1- Papillomavirus
2- Adeno virus
3- Hepatitis B virus
20

RNA viruses

1- Enveloped RNA viruses
A- Orthomyxoviruses
B- Paramyxoviruses
C-Retroviruses
E-Rhabdoviruses
F-Coronaviruses

2- Non-enveloped RNA

-Picornaviruses
21

Viral replication cycle

Viral population do not multiply by cell division because they are a cellular. Instead , they use the machinery and metabolism of a host cell to produce multiple copies of themselves and they assemble in the cell:-
Adsorption or attachment
Penetration.
uncoating and eclipse.
transcription or Replication.
assembly and release
22


1- Adsorption or attachment
of the virus particle to the specific receptors of the host cell plasma membrane.
Firm attachment requires the presence of receptors
for the virus on the plasma membrane (e.g. orthomyxoviruses and paramyxoviruses bind via an
envelope protein, known as haemagglutinin, to certain glycoproteins or glycolipids on the host cell)
23




24

2- Penetration or uptake

The process by which the virus or its genome enters the host cell cytoplasm. Penetration can be achieved by three separate Mechanisms:-

1-endocytosis

2-fusion
3-translocation
25

3. Uncoating and eclipse

After penetration, there is a period during which no intact infectious virus can be detected. This ‘eclipse phase’ begins with uncoating of the lipid membrane and protein capsid surrounding the nucleic acid viral core.
As uncoating proceeds, the viral nucleic acid becomes free to act as a template for the synthesis of virus mRNA
26


4- Transcription
. The virus mRNA codes for the synthesis of enzymes necessary to complete the process of uncoating itself and also to initiate early steps in viral replication.

When the virus initiates the reproductive cycle within the host cell, the synthesis of host cell RNA is halted, and host ribosomes are free to receive viral mRNA and provide a focus for transcription and synthesis of viral proteins.
27

5-Synthesis of viral components.

-Viral proteins are of two types:
-structural (the proteins that make up the virus
particle)
-non-structural (enzymes required for virus genome
replication).
-Structural viral proteins are synthesized on
cellular polyribosomes.
-There is a simultaneous synthesis of progeny viral nucleic acid, using newly synthesized nucleic acid polymerase
28

6. Assembly

Viral assembly is accomplished by incorporation of viral nucleic acid into putative
capsomeres – procapsids.
Assembly may occur in the cell nucleus, cytoplasm or (with enveloped viruses) at
the plasma membrane
29


7. Release
may occur either through gradual budding,
in the case of enveloped viruses, or by sudden
rupture.
30




31

Prions and prion diseases

Prions:-
(proteinaceous infectious particles) are unique elements in nature, and they are the agents of a group of chronic diseases called prion diseases or transmissible spongiform encephalopathies.
They infect essentially the nerve tissues of animals and humans, and manifest with long incubation periods lasting up to decades
32

The major features of

1-They are neither viruses nor viroids

2-Prions do not have either DNA or RNA

3-The native form of the prion protein, a normal constituent of healthy neural tissues, is designated PrPc, while the disease-related isoform derived from the latter is designated PrPScThe abnormal form, PrPSc, is derived from the native

4- precursor by a post-translational process leading to a conformational change from an α-helical structure to an insoluble β-sheet structure.
33

5-The abnormal (PrPSc) form resists destruction and accumulates in the neural tissues, causing vacuolation of cells, leading to a sponge-like appearance (hence the term ‘spongiform’)

6-The prototype prion agent caused scrapie, a central nervous system disease in sheep.

7-The prion agent can be transmitted to cows, mink, cats and mice, for instance, when fed with infected material.
8-Iatrogenic transmission of prion disease by neurosurgical instruments has been reported

34

Prion-induced diseases or transmissiblespongiform encephalopathies

Kuru
Creutzfeldt–Jakob disease
Fatal familial insomnia
35

Transmission

Kuru is transmitted in infected human brain by cannibalism.
The mode of transmission of CJD is mostly unknown.
There are a few reports of iatrogenic transmission by medical and surgical procedures.
hereditary acquisition occurs in familial cases.
contaminated food (beef from cattle with‘mad cow’ disease or bovine spongiform encephalopathy) is thought to cause acquired disease
36