Hepatitis B Virus Structure: Dane particle, filaments and spherical particles

Dr. Aizaz Author

Structure of Hepatitis B virus

https://youtu.be/vtl3ZTgcdpA

Hepatitis B virus is one of the major causes of Viral Hepatitis. Hepatitis means Inflammation of hepatocytes, the Liver cells.

In 1963, a supposedly new antigen was found in the Thalassemia patient of Australian descendent who frequently received blood transfusions. Initially, it was named “Australia Antigen” (Au). Later on, it was revealed that this Australian antigen is related to hepatitis B and it’s the part of its envelope (the outermost covering of virus) so it was named “Surface Antigen” of Hepatitis B virus (HbsAg).

When hepatitis B was discovered, scientists found spherules and tubular filamentous particles in the patient’s blood. Structurally these filamentous, as well as spherical particles, consists of lipid bilayer membrane along with surface antigen/proteins embedded into this membrane.

Scientists were very confused about the nature of the causative agent as they could not find any genome inside these spherical and tubular particles. They could only detect surface antigen that was called the Australian antigen at that time. They thought maybe it’s a prion disease.

In 1973, Dr. David Dane and his colleagues found the complete virion particle with the nucleocapsid in patients of Australian Antigen associated Hepatitis.[i] He also proved that this complete virus particle is the real culprit or infectious particle that caused Hepatitis B (previously known as Australia Antigen Associated Hepatitis). Spherules and filamentous particles were proved to be non-infectious by-products of the Hepatitis B virus.  In the honor of Dr. Dane, this complete, infectious hepatitis B virus particle was named “Dane particle”. Dane particles were much less frequently present in the blood of hepatitis B infected patients. If there are 1000 spherules and filaments, you may find 1 Dane particle. (1000:1 ratio). And because of this, it was not discovered earlier.

Actually, the spherules and filaments are nothing more than empty outer coverings (envelopes) of the hepatitis B virus.

1. Envelope

As you may have concluded by now that the Hepatitis B virus is an enveloped virus. Envelope is the outermost membrane. A virus steals the plasma membrane of the host as it comes out of the cell. It then decorates this stolen membrane with its viral proteins.

Hepatitis B virus decorates the envelope with surface proteins.

Surface proteins are of three types

1. Small Surface proteins: that solely consists of what we call; HBsAg, or S-antigen or S-subunit. It is a hydrophobic particle and most part of it is embedded into the membrane

2. Medium Surface proteins: along with S-subunits it also contains another particle called Pre-S2 subunit attach to the outer surface (extracellular) because of its hydrophilic nature.

3. Large Surface proteins consist of another particle Pre-S1 as well.

Small, medium, and large; all three may be present in the Dane particle.

These surface proteins are involved in attachment with certain receptors of hepatocyte membrane thus mediating the entry of the virus into the cell.

As another enveloped virus, the Hepatitis B virus can not tolerate the harsh environment. The outer envelop that is stolen from a modern host as a human can’t tolerate the hardships of the environment and is easily disrupted and surface proteins are lost thus rendering the virus harmless. Because of this reason Hepatitis B can not remain for long in a dry environment and is transmitted through blood or body fluids mainly (Semen or vaginal fluid).

 Naked or non-enveloped viruses have the host binding proteins embedded into the capsid (the inner coat of enveloped viruses but the outermost coat of naked viruses). The capsid proteins are indigenous viral proteins and they evolved millions of years back in the stressful environment of the past and are accustomed to that environment and are not easily destroyed. Hepatitis A virus, for example, is a non-envolped virus and is transmitted through the feco-oral route because it’s capsid can not only withstand the harsh environment of outside but also the fatally low pH of the stomach acid.

2. Nucleocapsid 

Inside the envelope is the nucleocapsid core of the hepatitis B virus. Capsid coat is made up of small repeating subunits called capsomers. The capsomer of the hepatitis B virus is called “Core” protein or Hepatitis B Core Antigen (HbCAg). It self-assembles itself in a beautiful icosahedral geometry.

3 .e Antigen

Between the capsid and the envelope, a small soluble protein is dissolved. It’s called the e-antigen.

Does “E” stand for the envelope????
No, “E” in e-antigen does not stand for “Envelope” or “early” as some people think. It has nothing to do with the envelope. Rather S-antigen can be called Envelope antigen, not this E-antigen.

In 1975 Dr. Magnius, found a new antigen along with Australia Antigen (S-antigen), in some patients of Hepatitis B. He arbitrarily and tentatively named it as E-antigen. [ii] He thought this name may be replaced by a more descriptive name in the future but that did not happen. Keeping in view the convention we still call it e-antigen. “E” stands for “E-antigen”. Nothing else!

As the hepatitis B virus replicates it continuously secretes e-antigen along with the spherules and filaments. This is a unique property of any virus.

The exact function of the e-antigen is not known. However, it is thought to have some role in suppressing the immune response against the hepatitis B virus. We will discuss it in a bit more detail in later lectures.

The Genome of the hepatitis B virus:

It is a DNA virus. DNA of the hepatitis B virus is circular, partially double-stranded DNA. One of the strands is complete while the other strand has gaps in it, it is not complete.

The length of the incomplete strand is quite variable. Some virus particles have nearly complete strands while others may have the strand with huge gaps in between.

Along with the DNA, Hepatitis B virus packs with it, it’s own personal DNA polymerase. It does not want to remain completely dependent upon the mercy of the host’s cellular machinery.

Why it has partially double-stranded DNA?

The Hepatitis B virus’s polymerase enzyme creates the new incomplete strand inside the cell, but before it completes the strand, the virus rushes out of the cell. Outside the cell, polymerase enzyme can not get the supply of raw material of DNA synthesis i.e. Nucleotides, so it can not complete the second strand. This incomplete strand is completed later when the virus re-enters the cell and then into the nucleus.

Because of the variable length of the incomplete strand, each virus particle has a variable weight or what they fancily call “Buoyant densities are variable”.

[i] Dane, D.S., Cameron, C.H. and Briggs, M. 1970. Virus-like Particles in Serum of Patients with Australia-Antigen-Associated Hepatitis. Lancet; i: 695-698.

[ii] Magnius LO, Espmark A. A new antigen complex co-occurring with Australia antigen. Acta Pathol Microbiol Scand B Microbiol Immunol. 1972;10:335–337.