HIV BASIC STRUCTURE AND CLINICAL IMPORTANCE
Here in this video I am going to explain the basic structure of HIV and some important clinical significance..
The complete sequence of the HIV-1 genome, extracted from infectious virions, has been solved to single-nucleotide resolution.HIV is different in structure from other retroviruses. It is around 120 nm in diameter (around 60 times smaller than a red blood cell) and roughly spherical.
HIV-1 is composed of two copies of noncovalently linked, unspliced, positive-sense single-stranded RNA enclosed by a conical capsid composed of the viral protein p24, typical of lentiviruses. The RNA component is 9749 nucleotides long and bears a 5’ cap (Gppp), a 3’ poly(A) tail, and many open reading frames (ORFs). Viral structural proteins are encoded by long ORFs, whereas smaller ORFs encode regulators of the viral life cycle: attachment, membrane fusion, replication, and assembly.
The single-strand RNA is tightly bound to p7 nucleocapsid proteins, late assembly protein p6, and enzymes essential to the development of the virion, such as reverse transcriptase and integrase. Lysine tRNA is the primer of the magnesium-dependent reverse transcriptase.The nucleocapsid associates with the genomic RNA (one molecule per hexamer) and protects the RNA from digestion by nucleases. Also enclosed within the virion particle are Vif, Vpr, Nef, and viral protease. A matrix composed of an association of the viral protein p17 surrounds the capsid, ensuring the integrity of the virion particle. This is in turn surrounded by an envelope of host-cell origin. The envelope is formed when the capsid buds from the host cell, taking some of the host-cell membrane with it. The envelope includes the glycoproteins gp120 and gp41, which are responsible for binding to and entering the host cell.
As the only proteins on the surface of the virus, the envelope glycoproteins (gp120 and gp41) are the major targets for HIV vaccine efforts. Over half of the mass of the trimeric envelope spike is N-linked glycans. The density is high as the glycans shield the underlying viral protein from neutralisation by antibodies. This is one of the most densely glycosylated molecules known and the density is sufficiently high to prevent the normal maturation process of glycans during biogenesis in the endoplasmic and Golgi apparatus.The majority of the glycans are therefore stalled as immature 'high-mannose' glycans not normally present on secreted or cell surface human glycoproteins. The unusual processing and high density means that almost all broadly neutralising antibodies that have so far been identified (from a subset of patients that have been infected for many months to years) bind to or, are adapted to cope with, these envelope glycans.
The molecular structure of the viral spike has now been determined by X-ray crystallography and cryo-electron microscopy.These advances in structural biology were made possible due to the development of stable recombinant forms of the viral spike by the introduction of an intersubunit disulphide bond and an isoleucine to proline mutation in gp41.The so-called SOSIP trimers not only reproduce the antigenic properties of the native viral spike but also display the same degree of immature glycans as presented on the native virus.Recombinant trimeric viral spikes are promising vaccine candidates as they display less non-neutralising epitopes than recombinant monomeric gp120 which act to suppress the immune response to target epitopes.