HEPATITIS C GROUP %

HEPATITIS C VIRUS
THE STRUCTUTRE,
DISCOVERY,TRANSMISSION, LIFE CYCLE






WRITTEN BY :
(212801)MUHAMMAD FAEZ AIMAN BIN MUHD AZAM
(211517)MUHAMMAD FAIZ BIN RAMLI
(212072)TAN SHING YI
(213029)AMALIA IZZATI BINTI ZULKARNAIN
(212734)JAMILAH JAZEERA BINTI SA'ARI

contents

03 THE STRUCTURE OF
04 HEPATITIS C VIRUS
05
06 An overview about defintion and
08 structure of Hepatitis C Virus to
people.

THE DISCOVERY OF
HEPATITIS C VIRUS

The timelapse of the discovery
of HCV and development of
treatment.

TRANSMISSION OF
HEPATITIS C VIRUS

An exposure of how Hepatitis C
Virus is transmitted into our
body

HEPATITIS C VIRUS LIFE
CYCLE

How does HCV produce inside
the host cell and its process

LIST OF REFERENCE

WHO
DISCOVER
HEPATITIS C?

DIFFERENCES BETWEEN HEPATITIS A , B AND C

HEPATITIS A is HEPATITIS B is caused by the HEPATITIS C is caused
hepatitis B virus (HBV) by the hepatitis C virus
caused by the (HCV)

hepatitis A virus

(HAV)

ROUTES OF Fecal-oral route. Percutaneous, mucosal, or Direct percutaneous
nonintact skin exposure to exposure to infectious
TRANSMISSION HAV is transmitted infectious blood, semen, and other blood. Mucous
body fluids. membrane exposures to
through: blood can also result in
HBV is transmitted primarily transmission.
- Close person-to through:
- Birth to an infected mother HCV is transmitted
person contact with - Sexual contact with an infected through:
person - Sharing contaminated
the infected person - Sharing contaminated needles, needles, syringes or
syringes or other injection-drug other equipment to
- Sexual contact equipment. inject drugs

with an infected

person

- Ingestion of

contaminated food

or water

Although viremia Less commonly through: Less commonly through:
occurs early in - Needle-sticks or other sharp - Birth to an infected
infection, instrument injuries mother
bloodborne - Organ transplantation and - Sexual contact with an
transmission of dialysis infected person
HAV is uncommon. - Interpersonal contact through - Unregulated tattooing
sharing items such as razors or - Needle-sticks or other
toothbrushes or contact with open sharp instrument
sores of an infected person injuries

INCUBATION 15-50 days 60-150 days 14-182 days
PERIOD (average: 28 days) (average: 90 days) (average: 14-84 days)

SYMPTOMS OF

ACUTE

INFECTION Symptoms of all types of viral hepatitis are similar and can include one or more

of the following:

THE 2020 NOBEL - Jaundice - Fever - Fatigue - Loss of appetite
PRIZE WINNER IN
PHYSIOLOGY OR - Nausea - Vomiting - Abdominal pain - Joint pain

MEDICINE POTENTIAL FORNone - Dark urine Chro-nCilcaiyn-fceocltoiorenddsetvoeollops in- D: iarrhCeharo(HniAcVchoinldlyre)n
5TH OCTOBER 2020 CHORONIC
INFECTION - 90% of infants after acute develops in over 50% of
AFTER ACUTE
INFECTION infection of birth newly infected people

- 25%-50% of children newly

infected at ages 1-5 years

- 5% of people newly infected as

adults

LIKELIHOOD OF- <30% of children - Most children <5 years of age do - Jaundice might occur
in 20%-30% of people
SYMPTOMATIC <6 years of age ≥not have symptoms - Nonspecific symptoms
(e.g., anorexia, malaise
ACUTE have symptoms - 30%-50% of people 5 years of or abdominal pain)
might be present in
INFECTION (which typically do age develop symptoms 10%-20% of people

not include - Newly infected

HEPATITIS C VIRUS (HCV) IS A SINGLE STRANDED jaundice) immunosuppressed adults

HCV IS TRANSMITTED THROUGH BLOOD - >70% of older generally do not have symptoms
TRANSFUSION AND INTRAVENOUS DRUG USE
UNLIKE HEPATITIS A. children and adults

have jaundice

TREATMENT - No medication - Acute: no medication available; - Acute: AASLD/IDSA
available best addressed through supportive recommend treatment
- Best addressed treatment of acute HCV without a
through supportive - Chronic: regular monitoring for waiting period
treatment signs of liver disease progression; - Chronic: over 90% of
antiviral drugs are available people with hepatitis C
can be cured regardless
REPRESENT HUGE HEALTHCARE AND ECONOMIC of HCV genotype with
BURDEN 8-12 weeks of oral
therapy

THE JOURNEY OF DISCOVERY HEPATITIS C

WHAT IS HEPATITIS C VIRUS (HCV) ???

Hepatitis C virus (HCV) is an enveloped, positive-strand RNA virus classified in the Hepacivirus
genus within the Flaviviridae family. The Flaviviridae family includes yellow fever virus, West Nile
virus, and dengue virus. The HCV particles are spherical and heterogenous in size, typically
ranging 40-80 nm in diameter. There are 7 HCV genotypes and 84 HCV subtypes currently
recognized. The intact HCV particle is often associated with lipoproteins (see Lipoviral Particles).

Consist of the E1 and E2 glycoproteins Composed primarily of cholesterol, cholesteryl
noncovalently associated as a heterodimer. esters, phosphatidylcholine, and sphingomyelin.
Structurally, the hypervariable region in the E2 Has a very high amount of incorporated
protein shields the E1 protein from the immune cholesterol, which gives it a composition that
system. resembles human very-low-density lipoprotein
Play a role in host receptor binding, (VLDL).
endosome-lipid membrane fusion, and It appears that cholesterol and sphingolipid both
assembly. play a role in the entry of HCV into host cells.

Consists of a single-stranded, Known as the HCV core, is the
positive-sense RNA approximately protein shell that encapsidates
9,600 nucleotide bases in length. and protects the HCV RNA.
Contains a single, long, open Made up entirely by the HCV core
reading frame (3,006-3037 codons) protein. The proteins on the outer
flanked by 5' and 3' untranslated surface of the core interact with
regions (UTRs). the viral membrane and inner
Used both for translation and surface binds to several HCV RNA
transcription. segments.
Following cleavage from the
polypeptide, the core proteins
assemble at the cytoplasmic face
of the endoplasmic reticulum to
form the capsid.

In the bloodstream, HCV can circulate as a hybrid lipoviral particle
that consists of lipoproteins tightly associated with the HCV
particle.
Include triglycerides, HCV RNA, capsid protein, E1 envelope
glycoprotein, E2 envelope glycoprotein, apolipoprotein B, and
apolipoprotein E.
Approximately 100 nm. The formation of the lipoviral particle
facilitates HCV entry into hepatocytes and it protects HCV from
antibody neutralization.

Tranmission Of Hepatitis C Virus in

8 WAYS

HCV is transmitted primarily through parenteral exposures to infectious
blood or body fluids that contain blood. Possible exposures include

01 Injection-drug use

02 Birth to an HCV-infected mother

Although less frequent, HCV can also be spread through:

03 Sex with an HCV-infected person (an inefficient means of
transmission, although HIV-infected men who have sex with
men have increased risk of sexual transmission)

04 Sharing personal items contaminated with
infectious blood, such as razors or
toothbrushes

05 Other health-care procedures that
involve invasive procedures, such as
injections

06 Receipt of donated blood,
blood products, and organs

07 Unregulated tattooing

08 Needlestick injuries in
health-care settings

HCV LIFE
CYCLE

HCV particles are 50–80 nm in
diameter and being associated

with neutral lipids and
apolipoproteins, which confers
them their unusually low buoyant

density

1 BINDING 4 TRANSLATION

-HCV will bind to 2 host receptors on the surface - Translation is initiated when ribosomal
of hepatocyte :- subunits bind to HCV RNA in the RER.
-The ribosome-RNA complex attached to RER
Density lipoprotein receptor (LDLr) membrane and translation of HCV polyprotein is
Heparin sulfate proteoglycans (HSPGs) complete. Approximately 3000 amino acids in
-Triggers the HCV outer heterodimer membrane one single polyprotein long.
protein to bind to scavenger receptor B1 (SRB1)
and tetraspanin protein CD81.
-Interaction between these two create a wave in

lipid membrane, propelling the HSV particle to a 5 PROTEOLYTIC PROCESSING
tight junction between hepatocytes.
Viral proteolytic process occur within the RER :
2 ENDOCYTOSIS Cellular protease cleave the core, E1, E2 and
p7 proteins.
-When the HCV reached tight junction, NS2 cysteine protease, in conjunction with
CD81 will interact with claudin-1(CLDN1), the N-terminal end of NS3 protein, cleaves
initiating inward folding of the viral from NS2 to NS3.
particle and hepatocyte cell membrane NS3 assisted by the membrane bound NS4A,
into a pit-like region covered by clathrin. forms NS3-4A protease complex that cleaves
-This process generates internal endosome the remaining proteins
compromised of a viral particle coated by
the host cell membrane Final resulting in 10 mature HCV protein
including structural and non-structural proteins.
3 FUSION AND UNCOATING

-When the viral enters the cell, the clathrin cage

surrounding the endosome disperse, leaving the

endosomonal vesicle free within the cytosol.

-Acidic pH within the endosome triggers the fusion

between the viral and the host membranes.

-This event allow the uncoating of the capsid shell

and the release of the HCV RNA into the cytosol for

translation and replication.

HCV LIFE CYCLE

RNA REPLICATION

-Several HCV proteins induce STEP

rearrangement of the host cell

06membranes to form the membranous
web.
-In the membranous web, the NS5B ASSEMBLY
RNA-dependent RNA polymerase -HCV particles assemble near

catalyzes the synthesis of a negative-
sense RNA intermediate (template) cytosolic lipid droplets (cLDLs)
that is used to create numerous copies forming the nucleocapsid that
of positive-sense progeny HCV RNA. consists of core proteins surrounding
-These newly synthesized HCV RNAs
are either incorporated into HCV RNA.
nucleocapsid particles or used for RNA -Once the core is formed, the
translation and replication. immature HCV particle fuses with a
luminal lipid droplet (LuLD) that is
loaded with ApoE proteins to create
a high-density HCV precursor.

-The ER synthesizes pre-very-low-

STEP density proteins (pre-VLDLs); the
high-density HCV precursor and the

MATURATION 07 pre-VLDL transit to the Golgi where
they mature prior to being packaged
-In the Golgi, the pre-VLDLs fuse with
and released.
large triacylglycerol (TG)-rich lipid


droplets to form VLDLs.

-The VLDLs then fuse with the high- STEP
density HCV precursors forming HCV
08
lipoviral particle.

-HCV lipoviral particle leaves the

trans-Golgi network (TGN) via RELEASE

multivesicular bodies. -Following transport of the

-The cellular secretory machinery
transports the multivesicular bodies multivesicular bodies that contain
to the cell surface.
the HCV lipoviral particles to the

cell surface, the vesicles fuse with

the hepatocyte cell membrane.

STEP -The generation of the HCV lipoviral

09 particle is coupled to the cellular
VLDL pathway and during this

process both HCV lipoviral particles

and VLDL particles are released into

the extracellular compartments.

.

LIST OF

REFERENCES

Hepatitis C | CDC. (2021, June 14). Centers for Disease Control and Prevention.
Retrieved November 22, 2021, from https://www.cdc.gov/hepatitis/hcv/index.htm
Hu, W. (2020, December 1). Hepatitis C: milestones from discovery to clinical cure.
Military Medical Research. Retrieved November 29, 2021, from
https://mmrjournal.biomedcentral.com/articles/10.1186/s40779-020-00288-y
Structure - HCV Biology - Hepatitis C Onlinee. (November 29, 2021).
https://www.hepatitisc.uw.edu/biology/structure
Life Cycle - HCV Biology - Hepatitis C Onlinee. (November 29, 2021). Retrieved
from: https://www.hepatitisc.uw.edu/biology/structure

THANK YOU