Gp120

Gp120

lowercase|title=gp120

gp120 is a glycoprotein exposed on the surface of the HIV envelope. The 120 in its name comes from its molecular weight of 120 kilodaltons.

The crystal structure of gp120 complexed to D1D2 CD4 and a neutralizing antibody Fab was solved by Peter Kwong in 1998. It is organized with an outer domain, an inner domain with respect to its termini and a bridging sheet. The gp120 gene is around 1.5 kb long and codes for around 500 amino acids [ [http://www.mcld.co.uk/hiv/?q=gp120 gp120 :: Molecules of HIV] ] . Three copies of gp120 form into a trimer that caps the end of gp41.

The Human Immunodeficiency Virus (HIV) can mutate frequently to stay ahead of the immune system. There is however a highly conserved region in the virus genome near its receptor binding site.The glycoprotein gp120 is anchored to the viral membrane through non-covalent bonds along with gp41, both coming from a cleaved protein, gp160. It infects any target cell with a CD4 receptor, particularly the helper T-cell, by binding to that receptor. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds.

The exact mechanism of virus entry into a cell is unknown. However, gp120 plays a vital role in seeking out receptors on host cells for entry.

gp120 targeted vaccines

Since CD4 receptor binding is the most obvious step in HIV infection, gp120 was among the first targets of HIV vaccine research. These efforts have been hampered by the chemical and structural properties of gp120, which make it difficult for antibodies to bind to it; also, it can easily be shed from the virus' surface and captured by T-cells due to its loose binding with gp41. This has traditionally been a hindrance in developing gp120 based HIV vaccines. However, a study published in the February 15, 2007 edition of Nature provides new promise in the field [Zhou, Tongqing et al. " [http://www.nature.com/nature/journal/v445/n7129/abs/nature05580.html Structural definition of a conserved neutralization epitope on HIV-1 gp120] ," "Nature" 445:732-737, 15 February 2007.] .The researchers have identified a region of susceptibilty in the gp120 glycoprotein that corresponds to a functional requirement for efficient association with CD4. This conserved region is involved in the metastable attachment of gp120 to CD4, and can potentially be targeted by the broadly neutralizing antibody b12. This study is promising in its prospects for developing a vaccine targeted at the invariant surface.

Research presented at the [http://www.aids2008.org/ 17th] International AIDS Conference in Mexico City suggested the possibility of a new vaccine based on antibodies that hydrolyze or cleave apart the gp120 proteinPlanque, S., Mitsuda, Y., Taguchi, H. et al., " [http://www.liebertonline.com/doi/abs/10.1089/aid.2007.0081 Characterization of gp120 Hydrolysis by IgA Antibodies from Humans without HIV Infection] ," "AIDS Research and Human Retroviruses", 23(12): 1541-1554, December 2007.] , rendering it incapable of binding to lymphocytesBrown, David, " [http://www.washingtonpost.com/wp-dyn/content/article/2008/08/07/AR2008080703223.html Antibodies May Lead to Protection Against HIV] ", "The Washington Post", 8 August 2008.] . This binding is the first step in the process of HIV infection. The antibody, IgA, is present in all human beings, but its potential for combating HIV was first recognized in patients with lupus, who exhibited both an abnormal resistance to HIV infection and an abnormally high concentration of IgA. Scientists confirmed in laboratory studies that IgA purified from the blood plasma and saliva of HIV-seronegative subjects effectively cleaved gp120, compared to the more naturally abundant IgG, which had little or no effect. To combat HIV, IgA could be adminstered in large doses as a drug to people already infected. However, to make an effective vaccine, scientists must find a way to stimulate the body to increase its own production of IgA. This has yet to be done.

Competition

The protein gp120 is necessary during the initial binding of HIV to its target cell. Consequently, anything which binds to gp120's target can block gp120 from binding to a cell by being physically in the way. Many of these are toxic to the immune system, such as the anti-CD4 monoclonal antibody OKT4.

EGCG, a flavonoid found in green tea, binds to the same CD4 receptor that gp120 binds to, effectively competing for this receptor. Test tube studies suggested that EGCG concentrations as low as 0.2 mmols/L – the amount of the molecule found in a cup or two of green tea – temporarily reduced HIV-CD4 cell binding by 40%. [ [http://www.aidsmeds.com/articles/1667_11621.shtml AIDSmeds.com - Top Stories : Green Tea for HIV? - by Tim Horn ] ] Substantial further research is needed both to confirm that this one-time laboratory experiment can be repeated successfully, and also to see whether it has any practical effect. For example, by binding to CD4, the flavonoid might slow HIV disease progression in a patient, but it might also attract an immune system-destroying antibody response against the non-human flavonoid. One important aspect of EGCG is that it can penetrate the blood brain barrier, where antiretroviral drugs cannot go, and may help prevent the onset of aids related dementia.

References

* http://www.aidsmap.com/en/docs/4406022B-85D7-4A9B-B700-91336CBB6B18.asp
* http://www.mcld.co.uk/hiv/?q=gp120
* http://www.ebi.ac.uk/interpro/IEntry?ac=IPR000777

ee also

* HIV structure and genome


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