Background
AIDS is acquired immunodeficiency syndrome, caused by the human immunodeficiency virus (HIV). HIV had become the discovery that it belonged to the human immunodeficiency virus genus Lentivirus (family Retroviridae). Its spherical particles between 90-130nm in diameter. From the research so far, we know that there are three types of human immunodeficiency virus, Type 1, Type 2 and Type O. The HIV-1 internal core consists of two RNA chains, core proteins p24, p17 and replication enzymes; while the external surface is the outer membrane of the virus, in which are housed the proteins gp120 and gp41. P24 protein is the major structure of HIV-1 protein capsid and hence we also call it HIV-1 capsid protein. The gene encoding P24 protein is HIV-1 structural gene gag. Studies have shown that the gag gene can encode the inner shell protein of the virus. When translated, a gag protein with a molecular weight of about 55kDa is first produced, and then the protein is decomposed into three proteins, p17, p24 and p15, under the action of proteases. Among them, p17 constitutes the inner membrane of the virus particle, p24 forms a firm cone-shaped shell surrounding the core of the virus, and p15 will continue to decompose into nucleocapsid proteins p9 and p7 that can bind to viral RNA. P24 forms an inner shell composed of about 1,200 shell particles in mature HIV virus particles, surrounding the outside of the viral core RNA and protecting the viral RNA. Due to the conservatism of the gag gene sequence, the amino acid sequence of one of its products, the p24 protein, is also highly conserved among HIV-1 strains.
Figure 1. Detection of HIV-1 p24 antigen based on immunoassay and selective recognition reaction. (Sources:Tang Z, et al. 2021)
HIV-1 patients can develop CD4+T lymphocyte-mediated immune response to p24 antigen in the initial phase of infection and form high-affinity antibodies. The antibodies generated won't become less sensitive to the conservative part of p24 antigen by mutation of the virus itself. Such antibodies can prevent MHC class II molecules from processing and presenting antigens and they can even prevent CD4+T lymphocytes from expanding. These two antibodies against the p24 antigen are isolated from peripheral blood from HIV-1 positive AIDS patients, researchers have found. A powerful inhibiter of the CD4+T lymphocyte proliferation was found for one antibody, and a moderate inhibitory effect was observed for the other antibody. The antigen epitopes the two antibodies detect are located at the N-terminus of the p24 protein. Anti-p24 antibodies can reduce the CD4+T lymphocytes' anti-HIV-1 immunity, as some studies have shown. CD8+T lymphocytes could elicit expression products for genes like pol, env, and gag. Once activated, CD8+T lymphocytes attack virus-infected cells and destroy the virus. They're the primary effector cells – cells that stop the body from reproducing, multiplying and transmitting viruses. They've determined that, just like CD4+T lymphocytes, CD8+T lymphocytes can also generate immune responses to P24 antigens, but only certain CD8+T lymphocytes can generate immune responses to epitopes on proteins; CD4+T lymphocytes do not. This type of response involving HLA I alleles, therefore, supports p24 antigen activation of effector CD8+T lymphocytes.
Laboratory testing methods for HIV include HIV antibodies, viral load, CD4+T lymphocytes, and p24 antigen testing. Once the body has caught HIV, p24 protein is an early HIV marker antigen that you can observe. You can see it 2 weeks after infection and the p24 level is at its peak 4 weeks later. And the body starts scrubbing away at anti-p24 antibodies. Since the antibodies destroy the free p24 protein in the blood and form a p24 antibody-antigen complex, the amount of detectable p24 antigen in the serum is still reducing, and will be less than the standard detection level after a while. Once the infection has progressed into the middle and late phases, the patient's immune system is attacked by the virus and the p24 antigen level will again increase, a manifestation of progressive HIV infection. Even today, testing labs mainly make HIV diagnoses for the first time by examining HIV antibodies in infected people's serum. Since the time lag (average of 2 months) for HIV antibodies to be detected, people with an early infection who haven't already developed antibodies are usually overlooked. When HIV-1 virus infects the host body, it makes p24 protein as the virus replicates. If the blood reveals p24 protein, early diagnosis can be accomplished and HIV's spread can be more effectively managed. We can also track the progress of the disease and the therapeutic effects of antiretroviral drugs by testing for p24 antigen. Additionally, infants of HIV-1 positive pregnant women can be antibody positive and obstruct the baby's diagnosis because the IgG antibodies present in the mother's blood can pass through the placenta to the baby. Thus, in addition to the nucleic acid test, the check for HIV status of the baby can also be done based on the presence of p24 antigen in the infant's serum. Currently, enzyme-linked immunosorbent assay, chemiluminescence detection (ECLIA), immune complex lysis detection (ICD) and nanotechnology-based biological barcode detection (BCA) are the most widely used antigen detection technologies for HIV-1 p24. Commercial detection reagents normally use double antibody sandwich ELISA for p24 antigen detection in the patient serum. Since ELISA method detection can be easily interfered with by other cross-substances present in the bloodstream, some immune blockers should be included in the ELISA analysis to prevent nonspecific reactions. Therefore, to enhance ELISA sensitivity towards the detection of p24 antigen, the antibody can be biotin-labeled, and the avidin-biotin-peroxidase complex method (ABC) is applied to enhance the signal to enhance ELISA sensitivity.
Alternative Names
Recombinant HIV-1 p24 Antigen
Recombinant Human Immunodeficiency Virus type 1 p24
HIV-1 p24 Recombinant Protein
Recombinant HIV-1 Core Protein p24
Recombinant HIV-1 Capsid Protein p24
Recombinant HIV-1 Gag Protein p24
References
- 1. Tang Z, et al. Fluorescence and visual immunoassay of HIV-1 p24 antigen in clinical samples via multiple selective recognitions of CdTe QDs. Mikrochim Acta. 2021, 188(12):422.
- 2. Tarosso LF, et al. Conserved HIV-1 Gag p24 Epitopes Elicit Cellular Immune Responses That Impact Disease Outcome. AIDS Res Hum Retroviruses. 2017, 33(8):832-842.