HIV stands for Human Immuno Deficiency Virus. It belongs to the group of Retrovirus which consist of positive single-stranded RNA. HIV was first isolated from the lymph node of the patient by Montagnier and Barre Sinoussi who won Nobel prize in the year 2008. The symmetry of HIV is icosahedral. Human Immuno Deficiency virus is enveloped and diploid. HIV belongs to the family Retroviridae and genus Lentivirus. It is a lethal virus that can cause life long effects by damaging the immunogenic cells like T-cells, macrophages, dendritic cells.
Among the immunogenic cells, the mainly affected cells by the Human Immuno Deficiency virus is CD4 cells. Human Immuno Deficiency virus damages the immune system by successive damage to the CD4 cells. HIV is a lentivirus which means “Slow virus” which takes time to make someone sick and it infects the cell in three stages namely acute stage, chronic latency stage and AIDs. There is a long interval between the primary infection and onset of AIDs.
Meaning of HIV
Human Immuno Deficiency virus can define as a virus that weakens the immune system which damages the CD4 cells which are a type of effector T-cells, that protects the body against the foreign body and cause various type of infections and disease.
Structure of HIV
Human Immuno Deficiency virus is a retrovirus which contains RNA as genetic material and is having a very complex structure and consist of the following structural components:
Outer envelope: The outer layer consists of lipid bilayer membrane that surrounds the matrix, protein capsid and the core material of the virus. It is embedded with many host cell proteins during the process of budding.
Nucleocapsid: The shape of the nucleocapsid is cone-shaped. The nucleocapsid is very dense and composed of 2,000 copies of the viral protein p24.
Matrix: It comprises of p17 viral protein and surrounds the nucleocapsid.
Genetic material: The genetic material of HIV contains two copies RNA as genetic material. The RNA of HIV is positively stranded. It is tightly bound with the Reverse transcriptase, Integrase, Ribonuclease and protease enzymes that perform different functions at the different stages of the viral infection.
Spikes: These are the filaments like structure which arises from an envelope by the ENV-enzyme. The spikes comprise of a cap which is composed of three molecules of gp120 and three molecules of gp41.
Genome organization of HIV
The genome size of HIV is 9.8 Kb. There are three structural and six regulatory genes found in the genome of HIV.
The primary function of HIV is to perform the structural synthesis of new viruses. There are three structural genes namely Gag, Env and Pol.
- Gag: It stands for “Group-specific antigen” and consists of p-7, p-17 and p-24 enzymes.
- Env: It stands for “Envelope” which consist of gp-160 proteins which break down into gp-120 and gp-41. Therefore, there are two subtypes of Env that is gp-120 and gp-41.
Gp-120: It is the extracellular protein which helps in binding with CD4 cells.
Gp-41: It is the transmembrane protein helps in the fusion of cellular and viral membranes.
- Pol: It stands for “Polymerase” which includes reverse transcriptase, integrase and protease enzymes.
There are six regulatory genes which regulate many functions at the time of host infection like replication, biosynthesis, virulence factors etc.
From six regulatory genes, two are involved in the process of RNA replication like:
- Tat: It helps in the transcription of the retroviral RNA.
- Rev: It helps in the transportation of the late mRNAs from the nucleus to the cytoplasm.
Apart from Tat and Rev genes, others are involved in providing virulency to the virus, biosynthesis and release of the virus. It includes the following genes:
- Nef: It decreases the expression of CD4 cells.
- Vif: It enhances virulence.
- Vpr: Transports the viral core from the cytoplasm to nucleus.
- Vpu: It enhances the virion release from the cell.
Life Cycle of HIV virus
The pathogenicity of the HIV, Includes the following steps:
Recognition of appropriate receptors: When HIV enters our body. It first recognizes the receptors and coreceptors present on the cell surface of CD4 T-cells. CCR-5 and CXCR-4 are the receptor and coreceptor respectively which present on the cell surface of CD4 cells. Therefore the virus envelope proteins which compose of gp-120 and gp-41 contact with the cell receptor of CD4 cell.
Attachment: After the recognition of specific binding sites, the gp-120 binds with the CD4 receptors. It promotes further binding with the co-receptor.
Conformational change: The binding of gp-120 to the receptor proteins creates a conformational change in the gp-120. This allows gp-41 to unfold and inserts its hydrophobic terminus on the host cell surface.
Fusion: The gp-41 then folds back on itself which draws the virus towards the cell and results into the fusion of two membranes i.e. virus envelope and cell membrane of CD4 cell.
Uncoating: This stage also refers to as “Insertion” or “Penetration”. After the fusion of virus and host cell membrane, the viral nucleocapsid enters into the host cell cytoplasm. The nucleocapsid contains RNA strands along with three essential replication enzyme namely restriction enzyme, integrase and protease.
Reverse transcription: It is the process of conversion of viral RNA into DNA by the reverse transcriptase. The reverse transcriptase enzyme contains two catalytic domain namely Ribonuclease H-active site and Polymerase active site. From polymerase active site, the ss-RNA transcribes into RNA-DNA double helix. Then, the ribonuclease H-active site breaks down the RNA.
Replication: After that, the polymerase active site completes the ss-DNA by the polymerization activity and forms a complementary strand of DNA to form a ds-DNA helix.
Integration: In this step, the viral ds-DNA enters into the host cell genome by the help of the integrase. Integrase comes into the action, which cleaves a di-nucleotide from DNA H3’ end of both the ends by producing sticky ends. Then the integrase enzyme transfers the DNA to the cell nuclease and facilitates the integration of viral DNA into the host cell genome. This process occurs inside the nucleus of the host cell.
Transcription: The cell then contains a viral DNA which undergoes transcription to form m-RNA. This m-RNA then moves from nucleus to the cytoplasm of the cell.
Translation: The m-RNA then undergoes translation which starts synthesizing the formation of building blocks or viral proteins for the new virus.
Processing: This involves the processing of viral proteins by the protease which cleaves the longer proteins to the smaller core proteins.
Reconstruction: At this stage, the RNA strands, reverse transcriptase, integrase and protease enzymes come all together and the core protein surrounds the capsid.
Budding: The immature virus particle releases out of the cell through the process of budding, which acquires a new envelope of viral protein. The virus then again undergoes maturation and infects other cells.
The HIV replicates billion of times by affecting the CD4 cells and progressively damages the immune system which makes the person prone to many infections.