Envelope glycoprotein GP120

Envelope glycoprotein GP120 (or gp120) is a

Gp120 is coded by the HIV

Since gp120 plays a vital role in the ability of HIV-1 to enter CD4⁺ cells, its evolution is of particular interest. Many neutralizing antibodies bind to sites located in variable regions of gp120, so mutations in these regions will be selected for strongly.[9] The diversity of env has been shown to increase by 1-2% per year in HIV-1 group M and the variable units are notable for rapid changes in amino acid sequence length. Increases in gp120 variability result in significantly elevated levels of viral replication, indicating an increase in viral fitness in individuals infected by diverse HIV-1 variants.^[10] Further studies have shown that variability in potential N-linked glycosylation sites (PNGSs) also result in increased viral fitness. PNGSs allow for the binding of long-chain carbohydrates to the high variability regions of gp120, so the authors hypothesize that the number of PNGSs in env might affect the fitness of the virus by providing more or less sensitivity to neutralizing antibodies. The presence of large carbohydrate chains extending from gp120 might obscure possible antibody binding sites.^[11]

The boundaries of the potential to add and eliminate PNGSs are naively explored by growing viral populations following each new infection.^[12] While the transmitting host has developed a neutralizing antibody response to gp120, the newly infected host lacks immune recognition of the virus. Sequence data shows that initial viral variants in an immunologically naïve host have few glycosylation sites and shorter exposed variable loops. This may facilitate viral ability to bind host cell receptors.^[13] As the host immune system develops antibodies against gp120, immune pressures seem to select for increased glycosylation, particularly on the exposed variable loops of gp120.^[14] Consequently, insertions in env, which confer more PNGSs on gp120 may be more tolerated by the virus as higher glycan density promotes the viral ability to evade antibodies and thus promotes higher viral fitness.^[15] In considering how much PNGS density could theoretically change, there may be an upper bound to PNGS number due to its inhibition of gp120 folding, but if the PNGS number decreases substantially, then the virus is too easily detected by neutralizing antibodies.^[12] Therefore, a stabilizing selection balance between low and high glycan densities is likely established. A lower number of bulky glycans improves viral replication efficiency and higher number on the exposed loops aids host immune evasion via disguise.^{[citation needed]}

The relationship between gp120 and neutralizing antibodies is an example of

The HIV viral protein gp120 induces apoptosis of neuronal cells by inhibiting levels of furin and tissue plasminogen activator, enzymes responsible for converting pBDNF to mBDNF.[23] gp120 induces mitochondrial-death proteins like caspases which may influence the upregulation of the death receptor Fas leading to apoptosis of neuronal cells,^[24] gp120 induces oxidative stress in the neuronal cells,^[25] and it is also known to activate STAT1 and induce interleukins IL-6 and IL-8 secretion in neuronal cells.^[26]

See also

• HIV envelope gene
• HIV entry to the cell
• gp41
• CD4
• CCR5
• Entry inhibitor
• Structure and genome of HIV

References