2. Hepatitis B virus:
Hepatitis B virus, is a common cause of liver disease and liver
cancer.
Hepatitis B virus, abbreviated HBV, is of the double stranded
DNA type, the genus is Orthohepadnavirus, and
Hepadnaviridae family viruses.
This virus causes the disease Hepatitis B.
3. Hepatitis B virus consists of an outer lipid envelope and an
icosahedral nucleocapsid core composed of protein.
The nucleocapsid encloses the viral DNA and a DNA
polymerase that has reverse transcriptase activity similar
to retroviruses.
The outer envelope contains embedded proteins (Antigens)
which are involved in viral binding, and entry into animal
cells.
HBV replicates through an RNA intermediate and can
integrate into the host genome.
4. The virus is one of the smallest enveloped animal viruses
with a virion is 42 nm in diameter, but pleomorphic forms
exist, including filamentous and spherical shape.
5. Genome:
The genome of HBV is made of circular DNA, but the DNA
is not fully double-stranded. The viral polymerase is
covalently attached to the 5′ end of the minus strand.
The genome is 3020–3320 nucleotides long.
Based on sequence comparison, HBV is classified into eight
genotypes, A to H. Each genotype has a distinct geographic
distribution.
6. The viral genome encodes four overlapping open reading frames
(ORFs: S, C, P, and X).
S ORF encodes the viral surface envelope proteins, the HBsAg,
and can be structurally and functionally divided into
1. L-HBsAg : large HBsAg
2. M-HBsAg: middle HBsAg
3. S-HBsAg: small HBsAg
7. The C ORF encodes either the viral nucleocapsid HBcAg.
The P ORF encodes the polymerase (pol) is a large protein
(about 800 amino acids).
The HBV X ORF encodes a 16.5-kd protein (HBxAg) with
multiple functions, including signal transduction, transcriptional
activation, DNA repair, and inhibition of protein degradation.
8. Replication:
After entry of the viral genome into the nucleus, the
single-stranded gap region in the viral genome is repaired
by the viral polymerase, and the viral DNA is
circularized to the covalently closed circular (cccDNA)
form.
9. The virus gains entry into the cell by binding to liver bile acid
transporter receptor (LBAT) or (NTCP) Na+-taurocholate co-
transporting polypeptide) This cell surface receptor necessary for
the entry of hepatitis B on the surface and being endocytosed.
The partially double-stranded viral DNA is then made fully double
stranded by a viral polymerase and transformed into covalently
closed circular DNA (cccDNA).
This cccDNA serves as a template for transcription of two type of
mRNAs i.e Largest pregenomic mRNA and the precore
mRNAs.
10. The largest mRNA, (which is longer than the viral
genome), is used to make the new copies of the genome
and the viral DNA polymerase.
The pregenomic RNA (pgRNA) serves as the template
for reverse transcription and the messenger RNA
polymerase.
The precore RNA directs the translation of the capsid
core protein.
11. The initial phase of HBV infection involves the
attachment of mature virions to host cell membranes,
likely involving the pre-S domain of the surface.
Mechanisms of viral disassembly and intracellular
transport of the viral genome into the nucleus are not
well understood and probably involve modification of
the nucleocapsid core protein
12.
13. Herpes Simplex Virus:
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known as
human herpesvirus 1 and 2 (HHV-1 and HHV-2), are two
members of the herpesvirus family, Herpesviridae, that infect
humans.
Under a microscope, the HSV1 and HSV2 strains look nearly
identical. They share approximately 85% of their genetic material.
14. Both HSV-1 (which produces most cold sores) and HSV-
2 (which produces most genital herpes).
Symptoms of herpes simplex virus infection include
watery blisters in the skin or mucous membranes of the
mouth, lips, nose or genitals.
15. HSV-1 is mainly transmitted by oral-to-oral contact to cause
oral herpes (which can include symptoms known as “cold
sores”), but can also cause genital herpes.
HSV-2 is a sexually transmitted infection that causes genital
herpes.
Both HSV-1 and HSV-2 infections are lifelong.
Most oral and genital herpes infections are asymptomatic.
Symptoms of herpes include painful blisters or ulcers at the
site of infection.
16. The structure of herpes viruses consists of a relatively large double-
stranded, linear DNA genome encased within an icosahedral protein
cage called the capsid, which is wrapped in a lipid bilayer called the
envelope.
The genome size of approximately 152 Kb
The envelope is joined to the capsid by means of aviral matrix (Viral
teguments) is a cluster of proteins that lines the space between the
envelope and nucleocapsid of all herpesviruses.
Herpes Simplex Virus:
17. • HSV-1 and HSV-2 each contain at least 74 genes (or open reading
frames, ORFs) within their genomes.
• These genes encode a variety of proteins involved in forming the
capsid and envelope of the virus.
• The envelope or lipid bilayer which contains twelve differnet
surface glycoproteins.
• Glycoproteins involved in the process of viral cell entry include
gB,gC,gD,gH, and gL, but only gB,gC,gD, and gH are required for
the binding of the HSV's envelope with the cellular membrane.
18.
19. Cellular entry:
The initial interactions occur when two viral envelope
glycoprotein called glycoprotein C (gC) and glycoprotein B
(gB) bind to a cell surface receptor called heparan sulfate.
Next, the major receptor binding protein, glycoprotein D
(gD), binds to three entry receptors present on the host cell
surface.
These cell receptors include herpesvirus entry mediator
(HVEM), nectin-1 and 3-O-sulfated heparan sulfate.
HSV must enter the host cell through means of fusion of its
envelope with the cellular membrane and finally enter in to
cell through endocytosis.
20. Replication:
The capsid travels along the cell to the nuclear pore where the viral
DNA is released. The linear genome enters the nucleus and
circularizes.
Once in the nucleus, the viral DNA is transcribed into mRNA by
cellular RNA polymerase.
In herpesviruses, viral gene expression is tightly regulated and
divided into 3 steps:
21. First step:
In the first step the immediate-early (IE or alpha) genes are
transcribed.
IE genes generally encode regulatory proteins.
An IE protein initiates transcription of the early (E or beta) genes.
Second step:
Early gene products are enzymes needed to increase the pool of
nucleotides and for viral replication.
Third step:
Lastly, late (L or gamma) genes are activated for production of viral
structural proteins.
22. After transcription in the nucleus, all mRNA transcripts are translated into
protein in the cytoplasm.
The translated proteins can go to the nucleus, stay in the nucleoplasm.
Capsid proteins assemble in the nucleus to form empty capsids.
After that full-length viral DNA is packaged to form nucleocapsids.
The nucleocapsids associate with segments of the nuclear membrane
where tegument and glycosylated envelope proteins have bound.
Enveloped virions accumulate in the endoplasmic reticulum (ER). Finally
mature virions are released by exocytosis.
23.
24. A concatemer is a long continuous DNA molecule that contains
multiple copies of the same DNA sequences linked in series.
Concatemers are frequently the result of rolling circle replication.
In the case of human herpesvirus the long concatemers are
subsequently cleaved between the pac-1 and pac-2 regions by
ribozymes when the genome is packaged into individual virions.
25. Treatment:
Antiviral medications, such as acyclovir, is the most effective
medications available for people infected with HSV.
These can help to reduce the severity and frequency of
symptoms, but cannot cure the infection.
Acyclovir is a new antiviral drug that acts as a specific
inhibitor of herpesvirus DNA polymerase
27. The Human Immunodeficiency Virus (HIV):
The human immunodeficiency virus (HIV) is a lentivirus (a
subgroup of retrovirus) that causes HIV infection.
HIV infects vital cells in the human immune system such as
helper T cells (specifically CD4+ T cells), macrophages, and
dendritic cells.
Family: Retroviridae
Genus: Lentivirus
28. HIV is an approximately 100 nm icosahedral structure with
72 external spikes that are formed by the two major
envelope glycoproteins gp120 and gp41.
Two major types of the AIDS virus, HIV- 1 and HIV-2, have
been identified. The major serological differences reside in
the surface protein gp120.
HIV-1 and HIV-2 are further separated into subtypes due
to the marked variability in the V3 (variable region) of the
gp120 protein.
29. The HIV-1 group M viruses predominate and are responsible
for the AIDS pandemic.
Group M can be further subdivided into subtypes based on
genetic sequence data. Some of the subtypes are known to be
more virulent or are resistant to different medications.
HIV-2 viruses are thought to be less virulent and transmissible
than HIV-1 M group viruses.
30. HIV has a characteristic dense, cone-shaped nucleocapsid
composed of the core protein p24.
The central core contains four viral proteins, p24 - the major capsid
protein, p17 - a matrix protein, The p7 and p9 are bound two
copies of the HIV RNA genome.
This nucleocapsid enclose two identical copies of the 9.8 kb single-
stranded positive RNA genome which are associated with the viral
enzymes reverse transcriptase (RT), RNase H, integrase and
protease.
The HIV genome contains three major genes, gag-pol-env,
encoding major structural proteins as well as essential enzymes.
31. Genes of HIV:
Group Specific Antigen (Gag): p24, p7, p17 and p9.
Envelope (Env): gp 120, gp 41.
gp120 binds to CD4 on CD4+ T lymphocytes and cells of the
monocyte/macrophage (CCR5 and CXCR4).
C-C chemokine receptor type 5 & C-X-C chemokine receptor type 4 ).
gp41 mediate fusion between the cellular and viral membranes.
Polymerase (Pol): Reverse transcriptase, integrase, protease.
Required for replication
Tat: Activation of transcription of viral genes
Rev: Transport of late mRNAs from nucleus to cytoplasm
32.
33. The HIV Life Cycle:
Binding and Fusion: HIV begins its life cycle when it binds
to a CD4 receptors (CCR5 and CXCR4) on the surface of a
CD4+ T-lymphocyte.
The first step in fusion involves the high-affinity attachment
of the CD4 binding domains of gp120 to CD4 receptors.
After HIV has bound to the target cell, the HIV enter into the
host cell through endocytosis.
34. Reverse Transcription:
After enters the into host cell, an enzyme called reverse
transcriptase liberates the single-stranded (+)RNA genome from
the attached viral proteins and copies it into a complementary DNA
(cDNA) molecule.
The process of reverse transcription is extremely error and the
resulting mutations may cause drug resistance or allow the virus
to escape from the body's immune system.
The reverse transcriptase also has ribonuclease activity that
degrades the viral RNA during the synthesis of cDNA, as well as
DNA-dependent DNA polymerase activity that creates a sense
DNA from the antisense cDNA.
35. Integration:
The newly formed HIV DNA enters the host cell's
nucleus, where an HIV enzyme called integrase
"hides" the HIV DNA within the host cell's own DNA.
Integrated HIV DNA is called provirus. The provirus
may remain inactive for several years, producing few or
no new copies of HIV.
36. Replication and Transcription:
The provirus uses a host enzyme called RNA polymerase to
create copies of the HIV genomic material.
During viral replication, the integrated DNA provirus is
transcribed into RNA, some of which then undergo RNA
splicing to produce mature mRNAs.
These mRNAs are exported from the nucleus into the
cytoplasm, where they are translated into the regulatory
proteins Tat and Rev (which encourages new virus production).
37. As the newly produced Tat and Rev protein accumulates
in the nucleus, it binds to full-length, unspliced copies of
virus RNAs and allows them to leave the nucleus.
Some of these full-length RNAs function as new copies
of the virus genome, while others function as mRNAs
that are translated to produce the structural proteins
Gag, Pol and Env.
38. Assembly:
An HIV enzyme called protease cuts the long chains of
HIV proteins into smaller individual proteins.
As the smaller HIV proteins come together with copies of
HIV's RNA genetic material, a new virus particle is
assembled.
39. Budding: The newly assembled virus pushes out from the host
cell.
During budding, the new virus steals part of the cell's outer
envelope.
This envelope, which acts as a covering, inserted with
protein/sugar combinations called HIV glycoproteins.
These HIV glycoproteins are necessary for the virus to bind
CD4 and coreceptors.
The new copies of HIV can now move on to infect other cells.
