# Pelinnur Acay - Hepatitis C Virus

# ****Hepatitis Viruses****

Hepatitis refers to inflammation of the liver.Usually caused by a viral infection.There are five major hepatitis viruses: hepatitis A, B, C,
D, and E virus (HAV, HBV, HCV, HDV, and HEV).

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# Types of Hepatitis
<img
src="https://i.imgur.com/XdqY98D.png" width="500"
height= "300" />
Figure 1.
(*Source*: Louten , J. (2016) . Hepatitis Viruses.
Essential Human Virology,p.213)

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# Hepatitis C Virus
HCV is one of several viruses in the Flaviviridae family. “Flavi” is Latin for “yellow,” because the family was named after yellow fever virus.
(Of course, HCV causes jaundice, too!)

Figure 2. HCV

Source = [MSD Manual](https:/https://www.msdmanuals.com/en-sg/professional/hepatic-and-biliary-disorders/approach-to-the-patient-with-liver-disease/jaundice/)
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# Molecular Properties of Hepatitis Viruses
<img
src="https://i.imgur.com/dUmywCC.jpg)" width="500"
height= "350" />
Figure 3.

Source= [SlideToDoc](https:/https://slidetodoc.com/what-is-viral-hepatitis-hepatitis-means-inflammation-of//)

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Figure 4. Reported Cases of Acute Hepatitis C

(*Source*: Louten , J. (2016) . Hepatitis Viruses.
Essential Human Virology,p.219)

HCV infection, with almost 30,000 new cases of HCV each year (Fig. 4). Over 12,000 people die each year of HCV-related liver diseases.

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# Hepatitis C Virus Virion
<img
src="https://i.imgur.com/t0XSstl.png" width="300"
height= "200" />
Figure 5. HCV is a small enveloped +ssRNA icosahedral virus. Electron micrograph courtesy of Maria Theresa Catanese, Martina Kopp, Kunihiro Uryu, and Charles Rice.

(*Source*: Louten , J. (2016) . Hepatitis Viruses.
Essential Human Virology,p.225)

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# Genome
<img
src="https://i.imgur.com/112qgqW.png" width="300"
height= "200" />
Figure 6. The HCV +ssRNA genome of 9.6kb has a 5′ NTR that contains an IRES for ribosome initiation of translation, a single open reading from that encodes a polyprotein, and a 3′ UTR with a poly(A) tail. The polyprotein is cleaved by cellular and viral proteases into 10 HCV proteins


Figure 7. HCV is an enveloped, icosahedral virus. The capsid is composed of the core protein, and E1 and E2 proteins are embedded into the viral envelope.

(*Source*: Louten , J. (2016) . Hepatitis Viruses.
Essential Human Virology,p.225)

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# HCV Viral Proteins
Figure 8. HCV viral proteins

* HCV Viral Proteins NS3, NS4A, NS4B, NS5A, and NS5B remodel the rough ER membrane, creating double- and multi-membraned vesicles where the genome is replicated.
* (A) This image was generated using 3D electron tomography. It shows several double-membrane vesicles (DMVs), including those highlighted with yellow letters, derived from the rough ER.
* (B) Shows the 3D reconstruction of the image in A. DMVs are in yellowish/light brown, the ER is in dark brown, the Golgi is in green, intermediate filaments are in blue, and single-membrane vesicles are in purple.

(*Source*: Louten , J. (2016) . Hepatitis Viruses.
Essential Human Virology,p.227)

# Entry
Figure 9. HCV Entry

HCV entry. HCV LVPs attach to the cell surface by interaction with HSPG, LDLR and SR-BI. SR-BI may delipidate HCV-associated lipoproteins and induces conformational changes in E2, exposing the CD81 binding site (step 1). TfR1 plays an unknown, post-CD81 role in HCV entry (not shown). Interaction of E2 with CD81 then activates signal transduction through EGFR and Ras as well as Rho GTPases (step 2). These signaling events promote lateral movement of CD81-HCV complexes to sites of cell-cell contact (step 3), interaction of CD81 with CLDN1, and HCV internalization via clathrin-mediated endocytosis (step 4). The low pH of the endosomal compartment induces HCV fusion (step 5).

Source = [NCBI](https:/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897199/#:~:text=Not%20the%20usual%20suspects%3A%20HCV,%2Dassociated%20apoE63%E2%80%9365./)

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# Translation

Figure 10 .

Noncanonical protein factors that modulate HCV RNA translation. On the left, the proteins are shown with their identified RNA-binding domains or motifs. The proteins are: La protein; NSAP1, NS1-associated protein 1; hnRNP L, heterogeneous nuclear ribonucleoprotein L; hnRNP D; IFG2BP1, Insulin-like growth factor 2 binding protein 1; LSm, Like-Sm-proteins 1–7; Gemin5 (involved in the SMN complex); PTB, polypyrimidine tract-binding protein; and PCBP2, Poly(rC)-binding protein 2. The RNA-binding domains depicted in dark gray are:
La motif domain; RRM, RNA recognition motif; acidic, acidic domain; SBM, short basic motif; KH, hnRNP K homology domain. On the right, the involvement of each protein in modulating the efficiency of translation of the HCV IRES is indicated (+, stimulatory; − inhibitory). Indirect interactions or those requiring further validation are marked with brackets.

Source =[Science Direct](https:/https://sci-hub.se/https://link.springer.com/chapter/10.1007/978-3-642-27340-7_6/)

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# Replication

Figure 11. HCV Replication

* HCV replication. In the process of attachment (1),
* HCV E1 and E2 proteins associate with at least four cellular proteins: CD81, SRB1,CLDN1, and OCLN, which initiates clathrin-mediated endocytosis (2).
* Following uncoating (3),
* The +ssRNA genome is translated into a polyprotein (4)
* That is cleaved by host proteases and viral proteases NS2 and NS3. Viral proteins remodel the rER membrane (5),
* Creating a membranous web of double- and multimembrane vesicles that become the site of genome replication. The RdRp NS5B creates the −ssRNA antigenome (6),
* That is used to create additional mRNAs or copies of the +ssRNA genome (7).
* And buds through the rER to obtain its envelope (9),
* Before being exocytosed (10)

(*Source*: Louten , J. (2016) . Hepatitis Viruses.
Essential Human Virology,p.226)

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# Assembly and Secretion

Figure 12. HCV Assembly and Secretion

Early events in the HCV lifecycle, including gene viral expression, recruitment of the viral RNA into an RNA replication complex, ER-retention of the E1-E2 glycoprotein and p7-NS2 complexes, and cPLA2-mediated trafficking of core dimers to cLDs, which are formed by the action of DGAT1. b. Late events in the HCV lifecycle. Viral RNA is shifted out of replication and translation and towards virus assembly. The interaction of p7-NS2 with NS3-4A recruits the viral core protein to the site of virus assembly. Virus particles assemble by recruitment of the E1-E2 glycoproteins and budding into the ER. c. The pathways of VLDL and HCV particle secretion, including maturation into low-buoyant density particles, perhaps through specific lipidation steps and/or interaction with maLDs, and the secretion of particles through the p7-buffered secretory pathway in HCV-infected cells.

Source = [NCBI](https:/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897199/#:~:text=Not%20the%20usual%20suspects%3A%20HCV,%2Dassociated%20apoE63%E2%80%9365./)

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