HIV: How does HIV invade my cells?

A virus is a parasite. It cannot survive on its own.

Viruses are not plants, animals, or bacteria, but they are the parasites of the living kingdoms. Viruses are not technically alive: They are like a brain without a body. So in order to make more copies of itself, a virus must hijack our cells and use them to make new viruses. Without a host cell, viruses cannot carry out their life-sustaining functions or reproduce.

A virus needs to reproduce to survive. If a virus reproduces itself, it is called replication. Well-known diseases caused by viruses are different types of flu, Ebola, small pox, HIV, Hepatitis, Rabies and Herpes to name a few.

The HIV virus uses CD 4 cells in the human body to replicate. CD 4 cells are white blood cells that play an important role in the immune system. Once a CD 4 cell is infected, it produces hundreds of new copies of new HIV particles. The replication cycle lasts 1-2 days and it is called the HIV life cycle.

Explanation of the HIV Cycle:

BINDING & FUSION

1.  The HIV virus enters the body

The HIV VIRUS

The HIV virus develop spikes made of glycoprotein on their envelopes  (outer membranes) that help them to attach to the surface of CD 4 cells.

A capsid is the protein shell of virus. The capsid encloses the genetic material  (RNA) of the virus. The capsid has three functions: 1) it protects the nucleic acid from digestion by enzymes, 2) contains special sites on its surface that allow the virion to attach to a host cell, and 3) provides proteins that enable the virion to penetrate the host cell membrane and, in some cases, to inject the infectious nucleic acid into the cell’s cytoplasm.

2.  The virus attaches itself to a T-helper cell  (CD 4 cell) and releases HIV into the cell

• CD 4+ T helper cells are white blood cells that are an essential part of the human immune system.  CD 4 is actually a glyco-protein found on the surface of immune cells like as T helper cells, monocytes, macrophages, and dendritic cells in the human body. They are often referred to as CD 4 cells, T-helper cells or T 4 cells.
• They are called helper cells because one of their main roles is to send signals to other types of immune cells, including CD 8 killer cells, which then destroy the infectious particle. If CD 4 cells become depleted, for example in untreated HIV infection, or following immune suppression prior to a transplant, the body is left vulnerable to a wide range of infections that it would otherwise have been able to fight.

The ARV medicine that block this process are called entry inhibitors.

CONVERSATION & INTEGRATION

3. Once inside the T-helper cell, HIV changes its genetic material so it can enter the nucleus of the cell and take control of it.

4.  After HIV attaches to the CD4 cell, it is absorbed into the main body of the cell. As this happens, HIV first loses its outer shell. This leaves viral capsid with HIV and three key enzymes (a type of protein) that HIV uses to replicate.

The ARV medicine that blocks this process are two different types of RT inhibitors (RTIs): (i) nucleoside/tide (NRTIs/NtRTIs), and (ii) non-nucleoside (NNRTIs).

5.  The new double-stranded HIV crosses into the central nucleus of the CD4 cell. This is where HIV is integrated into human DNA

The ARV medicine that block this process are called integrase inhibitors, abbreviated to INIs or INSTIs.

REPLICATION

6. The infected T-helper cell then produces more HIV proteins that are used to produce more HIV particles inside the cell.

The ARV medicine that block this process are called protease inhibitors.

ASSEMBLY, BUDDING & MATURATION

7.  The newly formed virus then has to leave the cell. The new HIV particles are then released from the T-helper cell into the bloodstream which infects other cells; and so the process begins again. The old CD4 cell then dies. This continuous process happens millions of times every day when not on ART. Without ART, HIV is one of the most active and rapidly reproducing virus.

Although there are currently no HIV drugs that block this stage, several drugs are in development. Budding inhibitors stop new HIV from leaving of the CD4 cell. Maturation inhibitors block the final assembly process.

Conclusion:

• An important concept about ART, is that HIV drugs only work on CD 4 cells in your body that are awake and actively producing HIV.
• However, most CD 4 cells in your immune system are sleeping or resting. The resting cells, even if they contain HIV, are not affected by ART.
• Reaching HIV in resting cells is a main aim in HIV cure research.

Important to know:

1. HIV uses CD 4 cells to replicate.
2. Different HIV medications block different stages of the HIV life cycle.
3. Each infected CD 4 cell produces about 300 new infectious viruses – called virions.
4. ART stops the HIV life cycle. On ART, the only virus in your body is in sleeping or resting CD 4 cells.
5. You need to continue taking ART every day because some of these sleeping cells wake up every day.

Acknowledgements:

• Dr Natasha Davies
• Dr Jackie Dunlop
• Dr Pappie Majuba
• Wits RHI Safer Conception Project
• Right to Care Training Department

https://micro.magnet.fsu.edu/cells/virus.html

http://i-base.info/guides/art-in-pictures/the-hiv-lifecycle-in-detail