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REPLICATION OF
VIRUSES
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INTRODUCTION:-
 As viruses are obligate intracellular pathogens they cannot
replicate without the machinery and metabolism of a host
cell.
 All viruses depend on cells for reproduction and metabolic
processes. By themselves, viruses do not encode for all of the
enzymes necessary for viral replication.
 But within a host cell, a virus can commandeer cellular
machinery to produce more viral particles.
 Bacteriophages replicate only in the cytoplasm, since
prokaryotic cells do not have a nucleus or organelles.
In eukaryotic cells, most DNA viruses can replicate inside the
nucleus, with an exception observed in the large DNA viruses, such
as the poxviruses, that can replicate in the cytoplasm. RNA viruses
that infect animal cells often replicate in the cytoplasm.
Although the replicative life cycle of viruses differs greatly
between species and category of virus, there are six basic stages for
the lytic cycle that are essential for viral replication.
Over all in virus replication mainly there is application of LYTIC
CYCLE AND LYSOGENIC CYCLE.
LYTIC CYCLE
LYSOGENIC CYCLE
 In actual viral replication differs from species and
category of viruses.
 This below listed six stages are important for viral
replication.
1)Attachment (ADSORPTION)
2)Penetration
3)Uncoating
4)Replication
5)Assembly
6)Virion release
Fig:- viral replication
FIG:- STEPS IN VIRUS REPLICATION
1) ATTACHMENT:-
 Glycoproteins in the viral lipid envelope or molecules on the
nucleocapsid (naked viruses) attach to specific receptor molecules
on the host cell.
 This viral-host receptor molecule relationship is often highly
specific. Accordingly, many viruses can only infect a limited range
of cells.
 For example, the human immunodeficiency virus (HIV)
preferentially infects T-helper cells as they express CD4 and
CXCR4 receptor molecules on their cell membrane. The
glycoprotein 120 molecule found in the lipid envelope of the HIV
is able to bind with these receptor molecules
2)Penetration:
 The process of attachment to a specific receptor can induce
conformational changes in viral capsid proteins, or the lipid
envelope, that results in the fusion of viral and cellular membranes.
 Some DNA viruses can also enter the host cell through receptor-
mediated endocytosis
 The mechanism by which viruses gain entry to their host cells is
dependent upon their structure; in particular, whether a lipid
membrane is present.
But differ in penetration or ENTRY to the :-
a. Enveloped virus:
Cytoplasmic membrane fusion: the virus fuses with the host cell
cytoplasmic membrane and the viral contents are then released into
the cytoplasm.
Endocytosis: the virus is engulfed by the host cell cytoplasmic
membrane.
b. Naked virus:
Direct: the virus passes directly across the host cell cytoplasmic
membrane.
Endocytosis.
3)Uncoating:
 The viral capsid is removed and degraded by viral
enzymes or host enzymes releasing the viral genomic
nucleic acid.
 Once inside the host cell, the viral lipid envelope or
capsid is shed and the viral nucleic acids are released.
 At this stage, the virus ceases to be infective and will only
regain infectivity after new virions have been formed
(eclipse phase).
4. Replication:
 After the viral genome has been uncoated, transcription or
translation of the viral genome is initiated.
 It is this stage of viral replication that differs greatly between DNA
and RNA viruses and viruses with opposite nucleic acid polarity.
This process culminates in the de novo synthesis of viral proteins
and genome.
 Viral replication is broadly a two-stage process; both viral
proteins and nucleic acid must be replicated to form new virus
particles.
A. VIRAL PROTEIN PRODUCTION
 Viruses must first transcribe their genetic material into messenger RNA (mRNA) in order to use host
ribosomes to produce new viral proteins.
 This process varies depending on the form and sense of the viral genetic material.
Forms:
– RNA: single-stranded (ssRNA) or double-stranded (dsRNA).
– DNA: double-stranded (dsDNA).
Sense:
– Sense (positive sense, +ve): genetic material is ready for translation, and is already equivalent to mRNA.
– Anti-sense (negative sense, -ve): genetic material requires transcription to mRNA before translation can
occur.
RNA:
-ve dsRNA and -ve ssRNA: use viral RNA polymerase to form +ve ssRNA, which is equivalent to mRNA.
+ve ssRNA: already equivalent to mRNA.
DNA:
DNA viruses have the equivalent of a positive and negative sense single strand.
They use host cell RNA polymerase to transcribe the negative sense strand into + ve ssRNA, which is
equivalent to mRNA.
B. VIRAL NUCLEIC ACID PRODUCTION
The mechanism of this process is also determined by the form and sense of the
viral genetic material.
RNA:
+ ve ssRNA and dsRNA: viral polymerase produces multiple – ve ssRNA, which
is transcribed into + ve ssRNA. With dsRNA, only the negative sense strand is
converted into + ve ssRNA.
– ve ssRNA: the inverse of the above process- viral polymerase produces multiple
+ ve ssRNA, which is then transcribed into – ve ssRNA.
DNA:
The viral genetic material is transcribed by viral DNA polymerase and then
incorporated into the host genome.
Host or viral DNA polymerase is then used to produce multiple viral genetic
material.
5)Assembly:
 After de novo synthesis of viral genome and proteins, which can
be post-transrciptionally modified, viral proteins are packaged
with newly replicated viral genome into new virions that are
ready for release from the host cell.
 This process can also be referred to as maturation.
 Viral progeny are formed by integrating the new viral proteins
and genetic material.
6. Release:
 There are two methods of viral release:
 lysis or budding.
 Lysis results in the death of an infected host cell, these types of viruses are
referred to as cytolytic. An example is variola major also known as smallpox.
 Enveloped viruses, such as influenza A virus, are typically released from the host
cell by budding. It is this process that results in the acquisition of the viral
phospholipid envelope. These types of virus do not usually kill the infected cell
and are termed cytopathic viruses.
 After virion release some viral proteins remain within the host’s cell membrane,
which acts as potential targets for circulating antibodies. Residual viral proteins
that remain within the cytoplasm of the host cell can be processed and presented
at the cell surface on MHC class-I molecules, where they are recognised by T
cells
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VIRUS REPLICATION STEPS

  • 2.
  • 3. INTRODUCTION:-  As viruses are obligate intracellular pathogens they cannot replicate without the machinery and metabolism of a host cell.  All viruses depend on cells for reproduction and metabolic processes. By themselves, viruses do not encode for all of the enzymes necessary for viral replication.  But within a host cell, a virus can commandeer cellular machinery to produce more viral particles.  Bacteriophages replicate only in the cytoplasm, since prokaryotic cells do not have a nucleus or organelles.
  • 4. In eukaryotic cells, most DNA viruses can replicate inside the nucleus, with an exception observed in the large DNA viruses, such as the poxviruses, that can replicate in the cytoplasm. RNA viruses that infect animal cells often replicate in the cytoplasm. Although the replicative life cycle of viruses differs greatly between species and category of virus, there are six basic stages for the lytic cycle that are essential for viral replication. Over all in virus replication mainly there is application of LYTIC CYCLE AND LYSOGENIC CYCLE.
  • 5.
  • 8.  In actual viral replication differs from species and category of viruses.  This below listed six stages are important for viral replication. 1)Attachment (ADSORPTION) 2)Penetration 3)Uncoating 4)Replication 5)Assembly 6)Virion release
  • 10. FIG:- STEPS IN VIRUS REPLICATION
  • 11. 1) ATTACHMENT:-  Glycoproteins in the viral lipid envelope or molecules on the nucleocapsid (naked viruses) attach to specific receptor molecules on the host cell.  This viral-host receptor molecule relationship is often highly specific. Accordingly, many viruses can only infect a limited range of cells.  For example, the human immunodeficiency virus (HIV) preferentially infects T-helper cells as they express CD4 and CXCR4 receptor molecules on their cell membrane. The glycoprotein 120 molecule found in the lipid envelope of the HIV is able to bind with these receptor molecules
  • 12. 2)Penetration:  The process of attachment to a specific receptor can induce conformational changes in viral capsid proteins, or the lipid envelope, that results in the fusion of viral and cellular membranes.  Some DNA viruses can also enter the host cell through receptor- mediated endocytosis  The mechanism by which viruses gain entry to their host cells is dependent upon their structure; in particular, whether a lipid membrane is present.
  • 13. But differ in penetration or ENTRY to the :- a. Enveloped virus: Cytoplasmic membrane fusion: the virus fuses with the host cell cytoplasmic membrane and the viral contents are then released into the cytoplasm. Endocytosis: the virus is engulfed by the host cell cytoplasmic membrane. b. Naked virus: Direct: the virus passes directly across the host cell cytoplasmic membrane. Endocytosis.
  • 14. 3)Uncoating:  The viral capsid is removed and degraded by viral enzymes or host enzymes releasing the viral genomic nucleic acid.  Once inside the host cell, the viral lipid envelope or capsid is shed and the viral nucleic acids are released.  At this stage, the virus ceases to be infective and will only regain infectivity after new virions have been formed (eclipse phase).
  • 15. 4. Replication:  After the viral genome has been uncoated, transcription or translation of the viral genome is initiated.  It is this stage of viral replication that differs greatly between DNA and RNA viruses and viruses with opposite nucleic acid polarity. This process culminates in the de novo synthesis of viral proteins and genome.  Viral replication is broadly a two-stage process; both viral proteins and nucleic acid must be replicated to form new virus particles.
  • 16. A. VIRAL PROTEIN PRODUCTION  Viruses must first transcribe their genetic material into messenger RNA (mRNA) in order to use host ribosomes to produce new viral proteins.  This process varies depending on the form and sense of the viral genetic material. Forms: – RNA: single-stranded (ssRNA) or double-stranded (dsRNA). – DNA: double-stranded (dsDNA). Sense: – Sense (positive sense, +ve): genetic material is ready for translation, and is already equivalent to mRNA. – Anti-sense (negative sense, -ve): genetic material requires transcription to mRNA before translation can occur. RNA: -ve dsRNA and -ve ssRNA: use viral RNA polymerase to form +ve ssRNA, which is equivalent to mRNA. +ve ssRNA: already equivalent to mRNA. DNA: DNA viruses have the equivalent of a positive and negative sense single strand. They use host cell RNA polymerase to transcribe the negative sense strand into + ve ssRNA, which is equivalent to mRNA.
  • 17.
  • 18. B. VIRAL NUCLEIC ACID PRODUCTION The mechanism of this process is also determined by the form and sense of the viral genetic material. RNA: + ve ssRNA and dsRNA: viral polymerase produces multiple – ve ssRNA, which is transcribed into + ve ssRNA. With dsRNA, only the negative sense strand is converted into + ve ssRNA. – ve ssRNA: the inverse of the above process- viral polymerase produces multiple + ve ssRNA, which is then transcribed into – ve ssRNA. DNA: The viral genetic material is transcribed by viral DNA polymerase and then incorporated into the host genome. Host or viral DNA polymerase is then used to produce multiple viral genetic material.
  • 19. 5)Assembly:  After de novo synthesis of viral genome and proteins, which can be post-transrciptionally modified, viral proteins are packaged with newly replicated viral genome into new virions that are ready for release from the host cell.  This process can also be referred to as maturation.  Viral progeny are formed by integrating the new viral proteins and genetic material.
  • 20. 6. Release:  There are two methods of viral release:  lysis or budding.  Lysis results in the death of an infected host cell, these types of viruses are referred to as cytolytic. An example is variola major also known as smallpox.  Enveloped viruses, such as influenza A virus, are typically released from the host cell by budding. It is this process that results in the acquisition of the viral phospholipid envelope. These types of virus do not usually kill the infected cell and are termed cytopathic viruses.  After virion release some viral proteins remain within the host’s cell membrane, which acts as potential targets for circulating antibodies. Residual viral proteins that remain within the cytoplasm of the host cell can be processed and presented at the cell surface on MHC class-I molecules, where they are recognised by T cells