Explanation of the structure of all the five types of hepatitis
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STRUCTURE OF HEPATITIS Presented by, Pavithra B R BSc Microbiology
INTRODUCTION
HEPATITIS Etymology – Greek (1700s)
HEPATITIS hepar = liver itis = inflammation
Hepatitis Virus
Hepatitis Alcohol Medical Conditions Medications
Types Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E
Structure Spreading
Severity Geographical Distribution
STRUCTURE
Hepatitis A Virus (HAV)
Genome of Hepatitis A Virus
Hepatitis A Virus Hepatitis A virus (HAV) belongs to the family Picornaviridae and genus Hepatovirus . It has a diameter of 27 nm. It is a non-enveloped virus (envelope is lipid covering). It has a capsid that is icosahedral in shape (i.e., 20 sided). The capsid is made up of subunits called Capsomeres. The capsomere is made up of 5 promoters. Each promoter is made up of 4 proteins - VP1, VP2, VP3 and VP4 which have a role in cell entry (VP - Viral Protein). Genome of HAV HAV is positive sense single stranded RNA and it consists of 7.5 kpb . The genome has an attached protein ' VPg '. VPg (Viral Protein Genome - linked). It is covalently attached to the 5' end of the RNA. The function of VPg is that it acts as a primer for the replication for copying the genome. The genome of the Virus is divided into 3 segments: P1, P2 & P3 (P - Polyprotein). The first segment encodes genes to make capsid proteins. The other 2 segments codes for non-structural proteins.
Hepatitis B Virus (HBV)
Genome of Hepatitis B Virus
Hepatitis B Virus Hepatitis B Virus (HBV) belongs to the family Hepadnaviridae and genus Orthohepadnavirus . It has a diameter of 47 nm and it is spherical in shape. It is an enveloped virus. It consists of an envelope which is protecting the virus. The envelope consists of HBsAg (Hepatitis B Surface Antigen) and it comes in the form of small HBsAg, middle HBsAg and large HBsAg. These antigens help to detect and attach to host cells as well as it has a role in diagnosis where the HBsAg is detected in the serum. It consists of a Capsid, that covers the genetic material and protects it and the shape is icosahedral with 27 nm diameter. The capsid carries an antigenic structure that is HBcAg (Hepatitis B Core Antigen). This is a special protein that helps the virus replicate and indicates that, indeed, replication is occurring. HBeAg (Hepatitis B Envelope Antigen) is present in between the capsid and the lipid envelope. This is considered to be non-particulate (not composed of distinct particles) and is secreted and accumulates in the serum.
Hepatitis B Virus Genome of HBV It consists of a partially double stranded circular DNA where one strand is long and one strand is short. The long strand is a complete strand and it is a negative strand which has a length of about 3,200 nucleotides, where as the complementary strand i.e., the short strand is a positive strand which has a length of about 1700 nucleotides. At the 5' end of the long negative strand there is a DNA polymerase (The HBV DNA polymerase) attached to it. The DNA polymerase is a multifunctional enzyme, it has both RNA-dependent and DNA-dependent polymerase functions which is involved in the replication cycle and also executes many functions including viral RNA binding, reverse transcription for DNA synthesis and RNA degradation. The genome has a compact structure with 4 overlapping genes which codes for different structural proteins. The S gene codes for the surface antigen (HBsAg). It consists of 3 regions the S region and 2 pre-S region (pre-S 1 and pre-S 2). This pre-S is basically a precursor molecule which might play a role in assembly of the HBsAg. The C gene codes for HBcGg . The P gene is the largest gene and it codes for the DNA polymerase enzyme. The X gene codes for a small non - particulate protein which leads to the enhanced replication of the Hepatitis B.
Hepatitis C Virus (HCV)
Genome of Hepatitis C Virus
Hepatitis C Virus Hepatitis C Virus belongs to the family Flaviviridae and genus Hepacivirus . It has a diameter of 60 nm and it is spherical in shape. It is an enveloped virus. It consists of a lipid membrane envelope. There are two molecules of glycoproteins which seems to protrude out from the envelope membrane – E1 and E2. The shorter one is E1 and the longer one is E2 (E - Envelope Glycoprotein). E1 and E2 are covalently bound by disulphide bonds. These glycoproteins play an important role in the interactions, the Hepatitis C has with the immune system. The N-terminal of the E2 is termed as Hyper-variable region 1 (HVR 1), HVR 1 helps E2 shield the virus from the immune system. Within the envelope there is Capsid which is icosahedron with diameter 30 - 40 nm and its function is to protect the genetic material. Genome of HCV HCV has a positive sense single - stranded RNA genome that is 9.4 kbp long. The genome consists of a single open reading frame (An ORF is a continuous stretch of codons that may begin with a start codon and ends at stop codon). This single open reading frame is translated to produce a single protein product, which is then further processed to produce smaller active proteins. At the 5' and 3' ends of the RNA are the untranslated region (UTR), that are not translated into proteins but they play a role in translation and replication of the viral RNA. The structural proteins made by the Hepatitis C Virus include Core proteins, E1 and E2; non-structural proteins include NS2, NS3, NS4A, NS4B, NS5A, and NS5B.
Hepatitis D Virus (HDV)
Genome of Hepatitis D Virus
Hepatitis D Virus Hepatitis D Virus is the only virus in the genus Deltaviridae . HDV is not classified into a viral family because it is a unique virus that is dependent on HBV. Two types of infection are recognized: Co-infection : Here delta and HBV are transmitted together at the same time. Co-infection clinically presents as acute hepatitis B, ranging from mild to fulminant disease. Superinfection : Here delta infection occurs in a person already harboring HBV. It is an enveloped virus. The envelope contains the HBsAg. The production and transmission of HDV is entirely dependent on the HBV to provide HBsAg. HDV is considered as satellite virus of HBV. However, the HDV does not share sequence similarity with HBV, and it can replicate independently of HBV. It has a diameter of 35 nm and it is special in shape. There is no distinct capsid structure for this virus but the genome is covered by large and small Hepatitis D Antigens or also called as Delta antigens. These are the only proteins encoded by Hepatitis D Virus. The large HDAg play a role in initiation of the viral genome replication and the small HDAg functions in the assembly of the new synthesized viral particles. Genome of HDV HDV has a negative sense single stranded circular RNA genome that is 1.7 kpbs long .
Hepatitis E Virus (HEV) ssRNA Capsid
Genome of Hepatitis E Virus
Hepatitis E Virus Hepatitis E Virus belongs to the family Hepeviridae and genus Hepeviris . HEV is a non-enveloped virus and it consists of a Capsid that is icosahedral with diameter 30 - 32 nm. Genome of HEV The genome of HEV is a positive sense single stranded RNA that is 7.2 kbps long. The genome contains 3 different ORF's which overlap with one another. The ORF 1 is situated at the 5' end which contains 5073 – 5124 nucleotides and it gives rise to non-structural proteins such as RNA-dependent RNA polymerase. The ORF 2 which is located at the poly A tail that is at 3' end contains 1977 – 1980 nucleotides which encodes the components of viral capsid. Overlapping with ORF 1 and ORF 2, ORF 3 is present which produce regulatory proteins.
CONCLUSION
Hepatitis A Hepatitis E Hepatitis D Hepatitis C Hepatitis B
Characteristics of Hepatitis Viruses Virus Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Family Picornaviridae Hepadnaviridae Flaviviridae Unclassified Hepeviridae Genus Hepatovirus Orthohepadnavirus Hepacivirus Deltavirus Hepevirus Virion 27 nm, icosahedral 42 nm, spherical 60 nm, spherical 35 nm, spherical 32 nm, icosahedral Envelope No Yes (HBsAg) Yes Yes (HBsAg) No Genome Ss(+)RNA dsDNA Ss(+)RNA Ss(-)RNA Ss(+)RNA Genome size (kb) 7.5 3.2 9.4 1.7 7.2 Infection Acute Chronic/ Acute Chronic/ Acute Chronic/ Acute Acute Incubation Period 2-7 Weeks 1-6 Months 1-5 Months 1-6 Months 2-9 Weeks Transmission Fecal -oral route Blood, Parental, Sexual Blood, Drug injections Blood, Parental, Sexual Fecal -oral route