What is the Structure of HIV?

Unlike most bacteria, HIV particles are too small to be seen through an ordinary microscope.

However they can be seen clearly with an electron microscope. Outside of a human cell, HIV exists as roughly spherical particles. HIV is spherical in shape and has a diameter of 0.1 microns (1/10,000 of a millimeter).

The outer coat of the virus, known as the viral envelope, is composed of two layers of fatty molecules taken from the membrane of a human cell.

When a newly formed virus particle buds from the cell it covers itself with the cell membrane (envelope is a common feature in animal viruses but uncommon in plant viruses).

Along with the proteins of host cell viral envelope, caries about 72 copies (on average) of a complex HIV protein known as Env. These Env copies protrude or spike through the surface of the virus particle.

Env consists of a cap made of three molecules called glycoprotein 120 (gpl20), and a stem consisting of three molecules called gyclycoprotein 41 (gp41) that anchor the structure in the viral envelope.

Within the viral envelope is a bullet-shaped core or capsid, made up of 2,000 copies of the viral protein – p24. The capsid surrounds two single strands of HIV RNA, each of which has a complete copy of the virus’s genes.

HIV has three structural genes – gag, pol, and env that contain information needed to make structural proteins for new virus particles. The env gene, for example, codes for a protein called gpl60 that is broken down by a viral enzyme to form gpl20 and gp41, the components of the env protein.

The remaining six genes of HIV are regulatory genes (tat, rev, nef, vif, vpr, and vpu) that contain information needed to produce proteins that control the ability of HIV to infect a cell, produce new copies of virus, or cause disease.

For instance the protein encoded by nef is apparently necessary for the virus to replicate efficiently, and the vpu-encoded protein influences the release of new virus particles from infected cells. Recently, researchers discovered that vif (the protein encoded by the vif gene) interacts with an antiviral defense protein in host cells (APOBEC3G), causing inactivation of the antiviral effect and enhancing HIV replication. This interaction may serve as a new target for antiviral drugs.

The ends of each strand of HIV RNA contain an RNA sequence called the long terminal repeat (LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell.

HIV’s core also includes a protein called p7, the HIV nucleocapsid protein. Three enzymes carry out later steps in the life cycle of virus. They are reverse transcriptase, integrase, and protease. Another HIV protein called pl7, or the HIV matrix protein, lies between the viral core and the viral envelope.

Binding and Fusion:

HIV entry into a host cell begins with gpl20 binding to CD4 receptor, which induces a conformational change in gpl20, exposing co receptor binding sites. After the chemokine coreceptor is engaged, the gp41 on the HIV surface undergoes a conformational change.

Conformational change in gp41 leads to formation of a stable structure that allows fusion of HIV and host cell membranes with a fusion pore, through which the viral core enters the host cell. These cores can utilize host cell microtubules to move toward the cell nucleus.

Reverse Transcription:

Once within the cell, the enzyme product of the pol gene, reverse transcriptase synthesizes linear double-stranded cDNA.

Integration:

The newly formed HIV DNA is then inserted into the host cell genomic DNA by the integrase enzyme of the HIV. The integrated HIV DNA is called provirus. The provirus may remain inactive for several years, producing few or no new copies of HIV.

Transcription:

When the host cell receives a signal to become active, the provirus uses a host enzyme called RNA polymerase to create copies of the HIV genomic material, as well as shorter strands of RNA called messenger RNA (mRNA).

The mRNA is used as a blueprint to make long chains of HIV proteins.

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.

Release by Budding:

Release of HIV from the host cell occurs in several steps. The p55 protein of HIV directs formation of a capsid (CA) protein that surrounds the RNA of HIV, a nucleocapsid (NC) protein that interacts with the RNA within the capsid, and matrix (MA) protein that surrounds the capsid and lies just beneath the viral envelope.

A protease enzyme encoded by the pol gene of HIV cleaves the large precursor proteins to produce the MA, CA, and NC proteins. Budding virions utilize host cell membrane to form the outer virion envelope of the budding virion that is necessary for production of infectious particles.

The process of viral budding relies on cellular endosomal sorting complexes required for transport (ESCRT) that sort proteins and form multivesicular bodies (MVBs). The newly assembled virus pushes out (“buds”) from the host cell.

During budding, the new virus steals part of the cell’s outer envelope. This envelope, which acts as a covering, is studded with protein/sugar combinations called HIV glycoproteins. These HIV glycoproteins are necessary for the virus to bind CD4 and co- receptors.

HIV virions released from infected cells may then enter the systemic circulation and be carried to widespread sites within the body to infect other cells.

Gpl20 is a glycoprotein exposed on the surface of the HIV envelope. The 120 in its name comes from its molecular weight of 120 kilodaltons. Gpl20 is essential for virus entry into cells as it plays a vital role in seeking out specific cell surface receptors for entry.