General Virus Replication Cycle
6 phases in viral replication cycle:
1) Attachment
2) Entry
3) Uncoat
4) Replication
5) Assembly
6) Release
1) Attachment
2) Entry
3) Uncoat
4) Replication
5) Assembly
6) Release
Virus Life Cycle- Growth Curve
During attachment , the virus will attach itself to the host cell receptor and gain entry to the cell. During eclipse, there will be a fall in virus titre when no infectious particles present during replication process and the virus will not be be detected in the external medium until released. During the release period, the virus will burst and new progeny virus will be assembled and released.
1) Attachment and Entry
Attachment is a specific binding between the viral capsid proteins and specific receptors (The receptors can be protein, carbonhydrate or lipid. ) on the host cell surface. This specificity also determines the host range of a virus. To infect the host cell, there must be a specific type for the virus to attach to. The virus is able to enter the host cell in 3 different routes:
-Endocytosis
-> Pinocytosis
-> Phagocytosis
-> Receptor-mediated endocytes
-Fusion
-Direct penetration
Endocytosis
Endocytosis is a process whereby the cells absorb material from outsdie the cell by engulfing it with their cell membrane.
Pinocytosis ( non specific ) is a form of endocytosis in which small particles are brought into the cell suspended within small vesicles which subsequently fuse with lysosomes to hydrolyze, or to break down, the particles.
Attachment is a specific binding between the viral capsid proteins and specific receptors (The receptors can be protein, carbonhydrate or lipid. ) on the host cell surface. This specificity also determines the host range of a virus. To infect the host cell, there must be a specific type for the virus to attach to. The virus is able to enter the host cell in 3 different routes:
-Endocytosis
-> Pinocytosis
-> Phagocytosis
-> Receptor-mediated endocytes
-Fusion
-Direct penetration
Endocytosis
Endocytosis is a process whereby the cells absorb material from outsdie the cell by engulfing it with their cell membrane.
Pinocytosis ( non specific ) is a form of endocytosis in which small particles are brought into the cell suspended within small vesicles which subsequently fuse with lysosomes to hydrolyze, or to break down, the particles.
Phagocytosis is the cellular process of phagocytes and protists of engulfing solid particles by the cell membrane to form an internal phagosome, which is a food vacuole.
Receptor-mediated endocytosis (RME), also known as clathrin-dependent endocytosis, is a process by which cells internalize molecules ( endocytosis ) by the inward budding of plasma membrane vesicles containing proteins with receptor site is specific to the molecules being internalized.
Uncoating
Nucleic acid has to be sufficiently uncoated that virus replication can begin at this stage. When the nucleic acid is uncoated, infectious virus particles cannot be recovered from the cell.
After uncoating
Virus genome will be sensitive to external environment:
-Mechanical shearing
-UV irradiation
-pH
-Dehydration
-Enzymes
The capsid and envelope will provide protection.
After uncoating, it ensures that the infection was successful.
Penetration
(A) Entry by fusing with the plasma membrane.
Nucleic acid has to be sufficiently uncoated that virus replication can begin at this stage. When the nucleic acid is uncoated, infectious virus particles cannot be recovered from the cell.
After uncoating
Virus genome will be sensitive to external environment:
-Mechanical shearing
-UV irradiation
-pH
-Dehydration
-Enzymes
The capsid and envelope will provide protection.
After uncoating, it ensures that the infection was successful.
Penetration
(A) Entry by fusing with the plasma membrane.
Some enveloped viruses fuse directly with the plasma membrane. Thus, the internal components of the virion are immediately delivered to the cytoplasm of the cell..jpg)
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(B) Entry via endosomes at the cell surface
Some enveloped viruses require an acid pH for fusion to occur and are unable to fuse directly with the plasma membrane. These viruses are taken up by invagination of the membrane into endosomes. As the endosomes become acidified, the latent fusion activity of the virus proteins becomes activated by the fall in pH and the virion membrane fuses with the end
osome membrane. This results in delivery of the internal components of the virus to the cytoplasm of the cellNon-enveloped viruses Non-enveloped viruses may cross the plasma membrane directly or may be taken up into endosomes. They then cross (or destroy) the endosomal membrane.
Stages in Virus Life Cycle
-Initiation of infection
-> Attachment and entry
-Replication and expression
-> Genome replication
->mRNA production, processing and translation
-Assembly and exit
-Viral Pathogenesis
Replication and expression
-Genome replication and gene expression are very closely linked
-Characteristics depends on nature of the genome
BALTIMORE CLASSIFICATION
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-Initiation of infection
-> Attachment and entry
-Replication and expression
-> Genome replication
->mRNA production, processing and translation
-Assembly and exit
-Viral Pathogenesis
Replication and expression
-Genome replication and gene expression are very closely linked
-Characteristics depends on nature of the genome
BALTIMORE CLASSIFICATION
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Regulation of Expression
Transcriptional control
-Promoters on viral genome
-Early and late activators / enhancers
-Late repressors
-Viral transciptases for RNA viruses not well understood
-Post-transcriptional control
-Splicing of polycistronic mRNA in nucleus
-Differential rate of splicing
Post-transcriptional control
-Control of mRNA from nucleus to cytoplasm
-Regulatory sequences found on introns
-Translational control
-Differential stability of mRNAs
-Secondary structures close to initiation sequence
-Problem due to overlapping reading frames
Translational control – overlapping reading frames
-IRES – internal ribosomal entry sites
-Frameshifting
-Pseudoknots
Translation of protein
Translation is the first stage of protein synthesis (part of the overall process of gene expression). It is also the production of proteins by decoding mRNA produced in transcription.
Transcriptional control
-Promoters on viral genome
-Early and late activators / enhancers
-Late repressors
-Viral transciptases for RNA viruses not well understood
-Post-transcriptional control
-Splicing of polycistronic mRNA in nucleus
-Differential rate of splicing
Post-transcriptional control
-Control of mRNA from nucleus to cytoplasm
-Regulatory sequences found on introns
-Translational control
-Differential stability of mRNAs
-Secondary structures close to initiation sequence
-Problem due to overlapping reading frames
Translational control – overlapping reading frames
-IRES – internal ribosomal entry sites
-Frameshifting
-Pseudoknots
Translation of protein
Translation is the first stage of protein synthesis (part of the overall process of gene expression). It is also the production of proteins by decoding mRNA produced in transcription.
Translation occurs in the cytoplasm where the ribosomes are located. Ribosomes are made of a small and large subunit which surrounds the mRNA. In translation, mRNA is decoded to produce a specific polypeptide. This uses an mRNA sequence as a template to guide the synthesis of a chain of amino acids that form a protein. Translation proceeds in four phases: activation, initiation, elongation and termination (all describing the growth of the amino acid chain, or polypeptidethat is the product of translation). Amino acids are brought to ribosomes and assembled into proteins.
Virus Assembly and Exit
Assembly depends on site of synthesis. There are different sites of protein synthesis and processing such as the endoplasmic reticulum and golgi body. There are also sites of assembly such as the nucleus, the endoplasmic reticulum and golgi body.
The cell from which the body itself buds from goes to survive, and sheds more viral particles. The lipid bilayer envelope of the viruses, is derived from the host cell itself and the sources of the envelope can be found in the nuclear membrane, endoplasmic reticulum, golgi body and plasma membrane.
Read more: http://knipelab.med.harvard.edu/pdfs/viral_capsids-Lucas.pdf
Budding
Budding is the process by which enveloped viruses acquire their external envelope, which bulges outwards and takes the virion inside. This method helps the virus leave the cell without lysing the cell, thereby allowing the cellular machinery to produce more viruses.
Assembly depends on site of synthesis. There are different sites of protein synthesis and processing such as the endoplasmic reticulum and golgi body. There are also sites of assembly such as the nucleus, the endoplasmic reticulum and golgi body.
The cell from which the body itself buds from goes to survive, and sheds more viral particles. The lipid bilayer envelope of the viruses, is derived from the host cell itself and the sources of the envelope can be found in the nuclear membrane, endoplasmic reticulum, golgi body and plasma membrane.
Read more: http://knipelab.med.harvard.edu/pdfs/viral_capsids-Lucas.pdf
Budding
Budding is the process by which enveloped viruses acquire their external envelope, which bulges outwards and takes the virion inside. This method helps the virus leave the cell without lysing the cell, thereby allowing the cellular machinery to produce more viruses.
Release
Virus may be released due to cell lysis, or, if enveloped, may bud from the cell. Budding viruses do not necessarily kill the cell. Thus, some budding viruses may be able to set up persistent infections. Not all released viral particles are infectious. The ratio of non-infectious to infectious particles varies with the virus and the growth conditions.
Virus may be released due to cell lysis, or, if enveloped, may bud from the cell. Budding viruses do not necessarily kill the cell. Thus, some budding viruses may be able to set up persistent infections. Not all released viral particles are infectious. The ratio of non-infectious to infectious particles varies with the virus and the growth conditions.
Viral Pathogenesis
To successfully infect a host, there must be sufficient to initiate the infection and a balance between viral replication, host defence and viral evasion of host defence.
To successfully infect a host, there must be sufficient to initiate the infection and a balance between viral replication, host defence and viral evasion of host defence.
To infect a host, the virus must first enter the body surface.
There are sites such as:
-Skins ( cuts, abrasion..etc)
Entry through this organ occurs when its integrity is breached by
breaks or punctures. Replication is usually limited to the site of entry because the epidermis is devoid of blood or lymphatic vessels that could provide pathways for further spread. Other viruses can gain entry to the vascularized dermis through the bites of arthropod vectors such as mosquitoes, mites, ticks, and sandflies. Even deeper inoculation, into the tissue and muscle below the dermis, can occur by hypodermic needle punctures, body piercing or tattooing, animal bites, or sexual contact when body fluids are mingled through skin abrasions or ulcerations.
Entry through this organ occurs when its integrity is breached by
breaks or punctures. Replication is usually limited to the site of entry because the epidermis is devoid of blood or lymphatic vessels that could provide pathways for further spread. Other viruses can gain entry to the vascularized dermis through the bites of arthropod vectors such as mosquitoes, mites, ticks, and sandflies. Even deeper inoculation, into the tissue and muscle below the dermis, can occur by hypodermic needle punctures, body piercing or tattooing, animal bites, or sexual contact when body fluids are mingled through skin abrasions or ulcerations.
-Conjuntiva ( eyelids )
The epithelium covering the exposed part of the sclera and the conjunctivae is the route of entry for several viruses. Every few seconds the eyelid passes over the sclera, bathing it in secretions that wash away foreign particles. There is usually little opportunity for viral infection of the eye, unless it is injured by abrasion. Direct inoculation into the eye may occur during ophthalmologic procedures or from environmental contamination (e.g., improperly sanitized swimming pools).
The epithelium covering the exposed part of the sclera and the conjunctivae is the route of entry for several viruses. Every few seconds the eyelid passes over the sclera, bathing it in secretions that wash away foreign particles. There is usually little opportunity for viral infection of the eye, unless it is injured by abrasion. Direct inoculation into the eye may occur during ophthalmologic procedures or from environmental contamination (e.g., improperly sanitized swimming pools).
-Urogenital tract
Some viruses enter the urogenital tract as a result of sexual activities. The urogenital tract is well protected by physical barriers, including mucus and low pH (in the case of the vagina). Normal sexual activity can result in minute tears or abrasions in the vaginal epithelium or the urethra, allowing viruses to enter. Some viruses infect the epithelium and produce local lesions (e.g., certain human papillomaviruses, which cause genital warts). Other viruses gain access to cells in the underlying tissues and infect cells of the immune system (e.g., human immunodeficiency virus type 1), or sensory and autonomic neurons (in the case of herpes simplex viruses).
-Respiratory tract
The most common route for a virus to enter.
Viruses may enter the respiratory tract in the form of aerosolized droplets expelled by an infected individual by coughing or sneezing, or through contact with saliva from an infected individual. Larger virus-containing droplets are deposited in the nose, while smaller droplets find their way into the airways or the alveoli. To infect the respiratory tract successfully, viruses must not be swept away by mucus,
neutralized by antibody, or destroyed by alveolar macrophages.
Some viruses enter the urogenital tract as a result of sexual activities. The urogenital tract is well protected by physical barriers, including mucus and low pH (in the case of the vagina). Normal sexual activity can result in minute tears or abrasions in the vaginal epithelium or the urethra, allowing viruses to enter. Some viruses infect the epithelium and produce local lesions (e.g., certain human papillomaviruses, which cause genital warts). Other viruses gain access to cells in the underlying tissues and infect cells of the immune system (e.g., human immunodeficiency virus type 1), or sensory and autonomic neurons (in the case of herpes simplex viruses).
-Respiratory tract
The most common route for a virus to enter.
Viruses may enter the respiratory tract in the form of aerosolized droplets expelled by an infected individual by coughing or sneezing, or through contact with saliva from an infected individual. Larger virus-containing droplets are deposited in the nose, while smaller droplets find their way into the airways or the alveoli. To infect the respiratory tract successfully, viruses must not be swept away by mucus,
neutralized by antibody, or destroyed by alveolar macrophages.
-Alimentary t
ract
ract
*click on pictures for bigger view.
Eating, drinking, and some social
activities routinely place viruses in the alimentary tract. It is designed to mix, digest, and absorb food,providing a good opportunity for viruses to encounter a susceptible cell and to interact with cells of the circulatory, lymphatic, and immune systems.
Virus shedding
-Absolutely necessary for survival; exceptions
-> spread through germ cells
-> consumption of infected tissue
-Effective transmission depends on
-virus concentration
-route of transmission
Modes of transmission
-Respiratory secretions
-> aerosols during speaking, sneezing and coughing
-> Virus can be inactivated by drying
-> It can be further transmitted by contaminated hands
-Saliva
-> Kissing
- Faeces
-> Resistant to drying
-Blood
-> Direct blood/ body fluids exposure