HIV Pathophysiology (2/3) - HIV Life Cycle

HIV is a single-stranded, positive-sense, enveloped retrovirus. Each virion is made up of a lipid bilayer with a capsid inside it containing two copies of an RNA genome, as well as reverse transcriptase, protease, and integrase. The viral envelope is derived from the lipid bilayer of a host cell and has glycoproteins sticking out of it necessary for the virus to infect cells. These glycoproteins, gp120 and gp41, together form gp160. A trimer with three pairs of gp120 and gp41 glycoproteins forms an envelope spike complex. The capsid is a protein shell that protects the genome. Reverse transcriptase, integrase, and protease get to work once HIV is inside a host cell, and we’ll get to that soon.
First, let’s follow HIV’s life cycle. Infection most commonly results from sexual contact, though it is also possible to contract HIV from contaminated needles or, in rare cases, from blood products such as blood transfusions. It is also possible for babies to get HIV from their mothers while in utero or from breastfeeding. Fortunately, you can’t get HIV from casual contact, the air, water, or mosquitos.
How Does HIV enter cells? Gp120 binds the CD4 glycoprotein. This triggers a conformational change that exposes binding sites for a coreceptor – either CCR5 or CXCR4. CCR5 is found on T-cells, macrophages, monocytes, and dendritic cells, while CXCR4 is found exclusively on T-cells. Anyway, further conformational changes reveal the fusion peptides of gp41. These fusion peptides are inserted into the host cell membranes, and HIV’s viral envelope can now fuse to it. The presence of both the CD4 glycoprotein and its coreceptor are essential for HIV to enter a host cell. Since almost all HIV-1 isolates are successfully transmitted using the CCR5 co-receptor, people with homozygous mutations in their CCR5 are basically immune to HIV, and even heterozygous mutations can slow the infection’s progression.
HIV’s single-stranded RNA gets reverse transcribed by reverse transcriptase into a double-stranded piece of DNA. As the reverse transcriptase goes about this process, the capsid uncoats. The double-stranded piece of DNA associates with integrase and is brought into the nucleus. There, integrase integrates the HIV DNA into the cell’s genome. This DNA is termed “proviral DNA” and viral RNAs get transcribed from it. Many other retroviruses wait until mitosis, when the nuclear membrane is broken down, to integrate their genome, but HIV interacts with proteins of the nuclear pore and gets admitted. Once HIV’s proviral DNA is integrated into the host cell’s genome, it cannot be eliminated except by killing the host cell. The viral DNA is transcribed and translated into viral polyproteins, which move to the surface of the cell and form an immature HIV. This HIV pushes itself out of the cell, grabbing part of the cell’s membrane to form the viral envelope. Protease comes in and cleaves the polyproteins at nine cleavage sites to create mature protein components. And we have a new HIV virion!

HIV graph based on: https://en.wikipedia.org/wiki/HIV#/media/File:Hiv-timecourse_copy.svg

Видео HIV Pathophysiology (2/3) - HIV Life Cycle канала Neural Academy