Different types of Viral replication, Stages of Viral replication

1. Molecular Biology of Viruses
Stages of Viral Cycle

2. Host Range
• Each virus has a different host range. The host range is the number of
different host cells a virus can infect.
• The attachment proteins on the outside of the virus determine the host range
for a virus. If they are compatible with proteins on the host cell membrane
found on many cells then the host range will be large. If the viral proteins are
only compatible with a protein found on a few host cell membranes then the
host range will be small.

3. The pathway (Routes)
• Lytic Cycle (fast)
• Lysogenic Cycle (slower)

4. Lytic Route
• The Virus hijacks the cell’s genetic machinery and start making copy
of it’s own genetic material.
• The Cell will make so much of the virus copy until it burst.
• The cell will burst by the process called lysis and the virus will be
released to infect another cells.
• Note: Sometimes there are not too many other host cell nearby,
remember that viruses are specific for different types of host cell, in
this case the slower lysogenic cycle is preferrable.

5. Lysogenic Route
• Instead of killing the host, the viral genetic information combines with the
host’s genetic information and becomes part of the host.
• The Host doesn’t even notice the change due to the repressor genes of the
viral genetic information which prevent it from being transcribed.
• It will just sit there in a dormant state.
• The host cell will be doing its normal functions and keeps replicating
without realizing that it is also including the viral genetic information (in all
of the cell’s daughter cells).
• The Virus will stay dormant until in something happens that weakens the
virus repressor gene the host genetic material then realizes something is
wrong and tries to repair it self.
• It will cut out its error which is the actually the virus.
• Due to that the virus will be released and will start replicating
• Will undergo lytic cycle, the cell will burst and the virus spreads out to other host
cell.

6. Viral Latency
• Latency happens after the entry stage. This Phenomenon happens before the mass production part of the synthesis.
• Not all viruses enter latency

7. Viral latency (Denoted as lysogenic part of
viral cycle)
• Viral latency is the ability of a virus to remain dormant within the host cell, sometimes
establishing lifelong occult infection. Depending on the virus, the trigger of latency is
highly variable but the host cell context is always determining. Latency can stop upon viral
genome reactivation, often promoted by stress cellular signals.
• The viral genome can remain latent either as an episome or integrated in the host
chromosome. The latter allows replication of the viral genome during host cell division.
Virus latency is generally maintained by a few viral genes that keep the viral genome silent
and escape from host immune system.
• Eukaryotic viruses like some Herpesviridae or retrofired are able to infect their host
lifelong thanks to latency. This gives them an enormous advantage for disseminating in
their host population: about 90% of human population would be infected with varicella-
zoster virus.

8. Episomal latency
• The Virus use of genetic episomes during latency. In this latency type, viral genes are stabilized, floating in
the cytoplasm or nucleus as distinct objects, either as linear or lariat structures.
• Example
- Herpesviridae (all members establish latent infection. Herpes virus include chicken-pox virus and herpes simplex
viruses (HSV-1, HSV-2), all members establish episomes in neurons and leave linear genetic material floating in the
cytoplasm.
- The Gammaherpesvirinae subfamily is associated with episomal latency established in cells of the immune system,
such as B-cells in the case of Epstein–Barr virus. Epstein–Barr virus lytic reactivation (which can be due
to chemotherapy or radiation) can result in genome instability and cancer. In the case of herpes simplex (HSV), the
virus has been shown to fuse with DNA in neurons, such as nerve ganglia or neurons, and HSV reactivates upon
even minor chromatin loosening with stress,although the chromatin compacts (becomes latent) upon oxygen and
nutrient deprivation.
- Cytomegalovirus (CMV) establishes latency in myeloid progenitor cells, and is reactivated by inflammation.
Immunosuppression and critical illness (sepsis in particular) often results in CMV reactivation.CMV reactivation is
commonly seen in patients with severe colitis.
• Advantages of episomal latency include the fact that the virus may not need to enter the nucleus, and hence may
avoid nuclear domain 10 (ND10) from activating interferon via that pathway.
• Disadvantages include more exposure to cellular defenses, leading to possible degradation of viral gene via cellular enzymes.
• Reactivation may be due to stress, UV, etc.

9. Proviral latency
• A provirus is a virus genome that is integrated into the DNA of a
host cell.
• Automatic host cell division results in replication of the virus's
genes, and the fact that it is nearly impossible to remove an
integrated provirus from an infected cell without killing the cell.
• This method is the need to enter the nucleus (and the need for
packaging proteins that will allow for that). However, viruses that
integrate into the host cell's genome can stay there as long as the
cell lives.
• One of the best-studied viruses that does this
is HIV. HIV uses reverse transcriptase to create a DNA copy of its
RNA genome. HIV latency allows the virus to largely avoid the
immune system. Like other viruses that go latent, it does not
typically cause symptoms while latent. Unfortunately, HIV in
proviral latency is nearly impossible to target
with antiretroviral drugs. Several classes of latency reversing
agents (LRAs) are under development for possible use in shock-
and-kill strategies in which the latently infected cellular reservoirs
would be reactivated (the shock) so that anti-viral treatment
could take effect (the kill).
There will be drawings in this side.

10. Maintenance
• Maintaining latency
• Both proviral and episomal latency may require maintenance for continued infection and
fidelity of viral genes. Latency is generally maintained by viral genes expressed primarily
during latency. Expression of these latency-associated genes may function to keep the
viral genome from being digested by cellular ribozymes or being found out by the immune
system. Certain viral gene products (RNA transcripts such as non-coding RNAs and
proteins) may also inhibit apoptosis or induce cell growth and division to allow more
copies of the infected cell to be produced.
• An example of such a gene product is the latency associated transcripts (LAT) in herpes
simplex virus, which interfere with apoptosis by downregulating a number of host factors,
including major histocompatibility complex (MHC) and inhibiting the apoptotic pathway.
• A certain type of latency could be ascribed to the endogenous retroviruses. These viruses
have incorporated into the human genome in the distant past, and are now transmitted
through reproduction. Generally these types of viruses have become highly evolved, and
have lost the expression of many gene products. Some of the proteins expressed by these
viruses have co-evolved with host cells to play important roles in normal processes.

11. Viral life cycle consists of six stages within the
host cell
• Attachment (Exhibits Host specificity and Cell tropism)
• Penetration
• Uncoating
• Multiplication/Synthesis
• Assembly
• Release

12. The Viral Entry:
Attachment, Penetration and uncoating

13. Types of Penetration and Uncoating
A. Direct Penetration
- Usually being done by Naked Viruses
(Viruses without envelope)
- Virus engulfed by endocytosis and either
the virus nucleic acid is pushed through the
vesicle membrane and into the cytoplasm
or the vesicle is lysed releasing the virion
B. Membrane Fusion
- The envelope of the virion fuses with the
host membrane and the nucleocapsid is
released into the cytoplasm. The capsid
protein and nucleic acids separate. Fusion is
generally promoted by a specific fusion
protein on the surface of the virion.
A. Endocytosis
- The Virion adsorbs to the host cell with its
protein spikes (Viral Proteins) and is
engulfed by endocytosis and is surrounded
by a vesicle. The envelope of the virion then
fuses with the vesicle membrane freeing
the nucleocapsid. The nucleic acids and
capsid proteins separate.
- Membrane Fusion and Endocytosis is
usually done by enveloped viruses.
Ligands and
Receptor
relationship
Receptor Mediated Endocytosis

14. Nuclear Entry
• Most DNA and few RNA viruses target their genome to
the host nucleus. The crossing of nuclear membrane
occurs in several ways :
• RNA virus, dsDNA virus and lentivirus genomes enter via
the nuclear pore complex (NPC) through the
cellular Importin transport.
• ssDNA virus capsid seems to be small enough to cross
the NPC and enter the nucleus as an intact capsid.
• Hepadnaviridae capsid would enter the NPC pore, but
remains attached to it and releases the viral genomic DNA
into the nucleoplasm.
• Herpesvirales capsid is too large to enter the NPC pore,
the viral genome is directly injected through the NPC on
which the capsid docks.
• All retroviridae except lentivirus would enter the nucleus
during mitosis, when the nuclear membrane temporarily
disintegrates.
All these strategies to cross the nuclear envelope barrier
are associated with various levels of capsid disassembly,
since virus can pass intact (e.g. parvoviridae) or, in the
case of injection, only the viral genome enters the
nucleus (e.g. herpesviruses). Genome integration in the
host genome may eventually follow .

15. The DNA Virus Synthesis :
Replications, transcription and translation.

16. Transcription and Translation of dsDNA Virus.
1. The Virus will go inside the cell or just drop off their
genetic material. (in this example the virus went inside
the cell).
2. Transcription: The Virus example is a DNA virus, the DNA
will go inside the Nucleus and exploiting RNA Polymerase
Enzyme the Nucleus make a thousands of copies of the
Virus DNA and transcribed it to mRNA.
3. Each of those mRNA will go to the Ribosomes outside the
Nucleus for translation.
4. Translation: mRNA will be translated to be the viral
proteins with the help of the Golgi Apparatus.
5. The mRNA will be Replicated and use the DNA
polymerase enzyme to Transcribe it to the Viral DNA.
Notes:
- Transcription: The creation of RNA from a DNA template.
- Viral proteins: The spikes, the capsid and Envelope (if applicable)
- DNA to RNA needs RNA Polymerase
- DNA to DNA needs DNA Polymerase
Example: Poxvirus, Herpes Virus
There will be drawings in this side.
We will doodle this animal cell during discussions

17. Transcription and Translation of ssDNA Virus.
• Viral ssDNA needs to be
converted to dsDNA in order for
the cell to replicate the virus.
• The virus will exploit the cellular
DNA Polymerase enzymes to
copy and transcribe themselves
into dsDNA.
• The dsDNA will now exploit the
cellular RNA polymerase to
convert the dsDNA to mRNA.
• The mRNA will be translated to
Viral proteins.
• The dsDNA will exploit the
Enzyme Cellular (DNA
Polymerase) to transcribe
dsDNA to ssDNA.
There will be drawings in this side.
We will doodle this animal cell during discussions

18. The RNA Virus :
Replications, transcription, translation, Assembly
and release.
Note: RNA VIRUSES always carry an ENZYME with them.
Enzymes look like
pacman 

19. Types of RNA Virus

20. Positive Sense RNA Virus (ssRNA)
• The way this virus is structured is simple. It
can easily be translated into protein (mRNA).
• The Virus RNA act as mRNA.
• When the virus is uncoated into the
cytoplasm and release the Viral RNA, that
Viral RNA does not need to enter the
Nucleus.
• That RNA (acting as mRNA) is directly
translated by the ribosomes of the cell.
• Translation: The Ribosome and the Golgi
apparatus will now translate those mRNA to
Viral proteins.
• The Question is How can our cell Produce
copies of the RNA?
• Positive Sense Viruses carry RNA replicase
Enzyme (a.k.a RNA dependent RNA
polymerase/RDRP
• The RDRP will copy and translate the +sense
RNA to -sense strand.
• The –sense strand will be used as a template to
produce +sense strands
Note:
Positive sense means “the virus makes sense for the cell” heheheh.
Host cell only have RNA polymerase and DNA Polymerase.
There will be drawings in this side.
We will doodle this animal cell during discussions

21. Negative Sense RNA (ssRNA) a.k.a Anti-sense RNA
(Example: Influenza virus)
• The problem with Negative Sense
RNA is when the Virion drop the
Genetic Material into the
Cytoplasm, the cell has no clue on
what to do with it.
• The Negative sense Strand
genome needs to be converted to
Positive Sense first in order for the
ribosomes to process it.
• Negative Sense Viruses also carry
RDRP Enzyme.
• RDRP will copy the negative sense
strand to positive sense strand used
as a template to produce
• Negative sense RNAs
There will be drawings in this side.
We will doodle this animal cell during discussions

22. Retroviruses RNA Virus
• Technically, this viruses are Positive Sense viruses.
• But, these RNA Viruses needs to convert and copy their viral RNA into
Viral DNA. Why?
• Because, these Viruses enter latency period. The type of latency is DNA
embedded latency.
• How do they convert their genome to DNA?
• These RNA Viruses have an enzyme with them (The enzyme Reverse
Transcriptase Enzyme)
• These RNA Viruses will drop off the RNA Virus and the RT Enzyme.
• RT Enzyme do the opposite of the transcription. (It takes RNA and Makes DNA
out of it)
Note: Implication; The RT enzyme makes the cell produce a lot of mistakes on
production of the cell, RNA viruses love it. Because those mistakes means
Mutation. RNA viruses is not easy to be controlled in terms of vaccination.
On the Other hand. The RT Enzyme is an easy target to create medication.

23. Double Stranded RNA Viruses
• dsRNA is basically 2 strands of
RNA virus composed of positive
and negative sense virus.
• The dsRNA Virus will use RDRP
Enzyme to transcribe dsRNA to
mRNA. mRNA will be translated
to Proteins.
• RDRP Enzyme will also be used
to create + and – strands and
fuse those 2 to make dsRNA
There will be drawings in this side.
We will doodle this animal cell during discussions

24. THE ASSEMBLY ANDS RELEASE OF VIRUS
• Putting the parts of the virus together.
• Assembly and release is the same with all the viruses. 

25. I will need to draw it because it is hard to
explain without drawing it. heheheh
• First drawing is Budding
(Done by Enveloped
Viruses. I will explain why
Viral Envelope is the same
with cell membrane
components)
• Lysis (Done by Naked
Viruses.)

26. Summary