Question

How does HIV evade the immune system? What cell does it “Hide” in?

Answer 1

• Human immunodeficiency virus (HIV) is the virus that causes acquired immunodeficiency syndrome (AIDS), a disease characterized by progressive deterioration of the immune system ultimately leading to death, usually from cancer or infection.
• HIV is a lentivirus, a type of retrovirus, or RNA-based virus. When the virus enters cells, its single-stranded RNA genome is reverse-transcribed into double stranded DNA by reverse transcriptase.
• Viral DNA is then imported into the nucleus and integrated into the cellular genome, where it reproduces. The success of HIV depends on its ability to evade the host’s immune system.

Evading cellular innate immunity

• HIV has a unique quality in that it does not alert the host’s innate immune defenses and does not induce type I interferon (IFN), a typical marker of antiviral response that inhibits viral replication and primes the adaptive immune system.
• This lack of IFN response seems to be critically important to the virus’s ability to evade the immune system. The uncoating of the virus and entry into the nucleus are critical steps in viral replication for evasion of innate immune sensors.
• One study identified a protein, cleavage and polyadenylation factor 6 (CPSF6), that, when truncated at its C-terminal end, restricts HIV-1 infection. In cells expressing CPSF6, nuclear entry was impaired.
• A single amino acid substitution within the viral capsid (CA) protein restored the ability of the virus to enter the nucleus. This mechanistically linked CA to the process of nuclear transport.
• Viruses with a mutation in CPSF6 trigger innate immune sensors leading to stimulation of IFN. Depletion of CPSF6 with short hairpin RNA expression also resulted in triggering of innate sensors and IFN production.
• Replication of the virus can be rescued by blocking the IFN receptor. A similar effect resulted in a virus strain deficient in cyclophilins (Nup358 and CypA), suggesting that HIV-1 evolved to use CPSF6 and cyclophilins to cloak its replication, allowing it to evade innate immune sensors and inducing an innate immune response.

What ceel does HIV hide ?

When a normal virus such as the common cold infects people we develop an immune response and produce defence cells which can quickly get rid of the virus. But when HIV infects us it can last for our whole life. HIV does this by successfully hiding from our immune cells, which are seeking to identify and destroy the virus, fooling them into thinking that it is part of the normal trash in a cell rather than being clearly visible on the cell surface.

"HIV can make a protein called Nef, which helps the virus hide. Nef interferes with one important part of our defences which helps our immune system recognise infected cells by displaying pieces of the infecting virus or bacteria on the cell surface, forming a target for our bodies' killer cells. When HIV infects one of our cells, the protein Nef binds to this helper system and alters it in such a way that the cell believes it belongs in the cellular trash bin rather than on the surface where our main defences can see it. The Nef protein made by HIV recruits other proteins which we naturally make within our cells to aid this subversion. These natural proteins and developed inhibitors which can block their actions, reversing the activity of Nef and potentially allowing our immune system to function properly and clear the virus from our system.