# Yağmur Ersazak-Human Immunodeficiency Virus (HIV)

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> [name=Yağmur Ersazak]

> [time=Tue, Jun 01 2021 8:00AM]

**HIV: [Virology by P. Saravanan, 2017]**
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# Human Immunodeficiency Virus (HIV)

## Classification and properties of HIV

* Family Retroviridae, a reverse transcriptase (Latin, retro = backwards)
* Two single-stranded RNAs (diploid)
* Only 2 of the 7 genera are considered to cause disease in humans:
1. BLV-HTLV retroviruses, including HTLV-I and HTLV-II
2. Lentivirus (Latin, lentus = slow) including HIV-1 and HIV-2

* Disease: Acquired immunodeficiency syndrome (AIDS)

**Figure 1: HIV Shape.**

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## Morphology of HIV

* A spherical enveloped virus approximately 90-120 nm in diameter
* Three-layer structure

**Figure 2: Structure of an HIV virion particle.**
Source:[hivbook.com](https://hivbook.wordpress.com/tag/structure-of-hiv-1/)

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* The outermost viral structure is the envelope. Two-component viral structural glycoproteins embedded in this lipid-based bilayer envelope yielded ends.
* gp120 outside and gp41 embedded in handle-shaped envelope attached to it.
* The gp120 tips on the envelope are trimeric, 72 grains.

**Figure 3: HIV virion**
Source:[basicmedicalkey](https://basicmedicalkey.com/human-immunodeficiency-viruses/)

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## HIV Genome

* The HIV-1 genome is about 9200 base pairs in length.
* The "gag" gene in the genome of HIV-1 synthesizes the precursors of virion capsid proteins, the "pol" gene synthesizes the precursors of many virion enzymes, and the "env" gene synthesizes the precursors of the envelope glycoproteins.


**Figure 4: HIV genome.**

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**Figure 5: HIV gP 120.**

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* It carries out its different stages in its life cycle through its 15 proteins made by 9 genes.

**Table 1: Gene and gene products of HIV.**


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**Table 2: The continuation of gene and gene products of HIV.**

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## Molecular Characterization of HIV

* Based on the heterogeneity of the HIV RNA, three groups are recognized in HIV-1:
1. M (major/main),
2. N (non-M, non-O/new)
3. O (outlier)

**Table 3: Major antigens of HIV-1 and HIV-2.**

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## HIV Lifecycle

### Attachment

The protein found in the outer envelope of HIV is strongly attracted by CD4+ surface receptors located outside the T4 cell. After HIV binds to the CD4+ surface receptor, it activates other proteins on the cell surface. Thus, the cell surface and HIV are completely combined.

**Figure 6: HIV Attachment.**
Source: [ncbi](https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/tileshop_pmc_inline.html?title=Click%20on%20image%20to%20zoom&p=PMC3&id=3405824_cshperspectmed-HIV-006866_F1.jpg)

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### Reverse Transcription

After cell attachment, the viral capsid is released into the host cell. A viral enzyme called reverse transcriptase makes a DNA copy of RNA. This new DNA created by the virus is called "proviral DNA".

### Integration

HIV DNA is transported to the cell nucleus, which is the center of the cell and contains the cell's own DNA. Then, the proviral DNA is hidden inside the DNA of the cell by means of a viral enzyme called integrase.

**Figure 7: HIV Entry Process**
Source: [Nature Reviews](https://www.nature.com/articles/nrmicro.2016.162)

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### Transcription

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

### Translation
mRNA works for the production of new viral proteins. Each part of the mRNA communicates with the protein building blocks to make the parts of HIV.

As each mRNA sequence is processed, the corresponding protein sequence is produced. This process continues until the mRNA sequence converts or translates the new viral proteins needed to produce new viruses.

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**Figure 8: Model for HIV Transcriptional Regulation**
Source:[researchgate](https://www.researchgate.net/figure/Model-for-HIV-Transcriptional-Regulation-During-initiation-of-HIV-transcription-RNAP-II_fig2_259771678)

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### Assembly and Release

An HIV enzyme called protease splits long chains of HIV proteins into smaller individual proteins. As smaller HIV proteins assemble with copies of HIV's RNA genetic material, a new virus particle is assembled.

### Maturation

Shortly after virus budding release from the cell, the viral protease cleaves the Gag precursor into the mature Gag proteins MA, CA, NC and p6. Gag processing is a highly ordered multistep sequential process that triggers the morphological rearrangement of viral protein structure, which is known as maturation.

**Figure 9: HIV-1 assembly, release and maturation**
Source:[researchgate](https://www.researchgate.net/figure/Schematic-overview-of-HIV-1-assembly-release-and-maturation-Translated-protein-along_fig22_280699833)

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**Figure 10: The life cycle of HIV-1.**
Source: [researchgate](https://www.researchgate.net/figure/The-essential-steps-in-the-life-cycle-of-HIV-1-The-first-step-is-the-attachment-of-the_fig1_236183663)

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## HIV Latency

HIV-1 Latency can be seen in a number of different anatomical regions as well as in multiple immunological cell types. The latent virus is not detected by the host immune system or does not respond to antiretroviral therapy; in addition, upon reactivation, the virus may be expressed and infection may persist.

**Figure 11: HIV Latency.**
Source: [asm.org](https://jvi.asm.org/content/94/3/e00375-19)

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## HIV Immunopathogenesis

* Natural immune response in acute infection is the first line of defense against the pathogen.
* The region where anatomical barrier is exceeded are mucosal surfaces.

**Figure 12: Virulence and Pathogenesis of HIV-1 Infection.**
Source: [sciencemag.org](https://science.sciencemag.org/content/343/6177/1243727/F3)

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## Markers of HIV diagnosis

After HIV infection, the order of blood markers to identify infection in chronological order of appearance is: viral RNA, p24 antigen, and antibody to HIV antigens.

**Figure 13: Trajectories of HIV-RNA viremia, CD4 T cells, p24 antigen and HIV antibody in the early stage of HIV infection.**
Source:[researchgate](https://www.researchgate.net/publication/281679961_Overcoming_the_challenge_of_diagnosis_of_early_HIV_infection_A_stepping_stone_to_optimal_patient_management/figures?lo=1)

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