The P24 capsid protein is the most abundant HIV protein with each virus containing approximately 1,500 to 3,000 p24 molecules. [1] It is the major structural protein within the capsid, and it is involved in maintaining the structural integrity of the virus and facilitating various stages of the viral life cycle, including viral entry into host cells and the release of new virus particles. [2] Detection of p24 protein is used in various diagnostic assays, including antigen tests, to identify the presence of HIV in a person's blood. [3] These tests are designed to detect viral antigens, such as p24, only in the acute phase of HIV infection. After approximately 50 days of infection, the p24 antigen is often cleared from the bloodstream entirely. [4]
P24 has a molecular weight of 24kDa and is encoded by the gag gene. The structure of HIV capsid was formed by X-ray crystallography and cryo-electron microscopy. [5] p24 capsid protein consists of two domains: the N terminal domain and the C-terminal domain connected by flexible inter-domain linkers. The N-terminal domain (NTD) is made up of 7 α-helices (H) and β-hairpin. [6] [7] The C-terminal domain (CTD) has 4 α-helices, and an 11-residue unstructured region. [8] [9] The N-terminal domain (NTD) facilitates contacts within the hexamer, while the C-terminal domain (CTD) forms dimers that bind to adjacent Hexamers. [10] Each hexamer contains a size-selective pore surrounded by six positively charged arginine residues, and the pore is covered by a β-hairpin that can undergo conformational changes, either opening or closing it. [11] Stabilizing the hexamer, an IP6 molecule binds to the pore's center. Additionally, the C-terminal domain includes a Major Homology Region (MHR) spanning amino acids 153 to 172 with 20 highly conserved amino acids. [12] Moreover, the N-terminal domain features a loop (amino acids 85–93) that interacts with cyclophilin A or Cyp A.
P24 is a structural protein that plays a crucial role in the formation and stability of the viral capsid, which protects the viral RNA. The role of p24 capsid protein can be identified in the different stages of the HIV replication process.
The HIV-1 p24 capsid protein plays crucial roles throughout the viral replication cycle, making it an attractive therapeutic target. Unlike the viral enzymes (protease, reverse transcriptase and integrase) that are currently targeted by small-molecule antiretroviral drugs, p24 capsid proteins operates through protein-protein interactions. Capsid inhibitors, such as Lenacapavir and GS-6207, interfere with the activities of the HIV capsid protein and underwent evaluation in phase-1 clinical trials as monotherapies. [13] [14] They demonstrated anti-viral activity against all subtypes with no cross-resistance with current antiretroviral drugs. [13] [14] These findings support therapies aimed at disrupting the functions of the HIV capsid protein.
P24 can induce cellular immune responses and has been included in some vaccine strategies. [3]
P24 is a target for the immune system, and antibodies against p24 are used in diagnostic tests to detect the presence of HIV antibodies. Fourth-generation HIV immunoassays detect viral p24 protein in the blood (as well as patient antibodies against the virus). Previous generation tests relied on detecting patient antibodies alone; it takes about 3–4 weeks for the earliest antibodies to be detected. The p24 protein can be detected in patient blood as early as 2 weeks after HIV infection, further reducing the window period necessary to accurately detect the HIV status of the patient. [15]
The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.
A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. After invading a host cell's cytoplasm, the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome, the reverse of the usual pattern, thus retro (backwards). The new DNA is then incorporated into the host cell genome by an integrase enzyme, at which point the retroviral DNA is referred to as a provirus. The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes, producing the proteins required to assemble new copies of the virus. Many retroviruses cause serious diseases in humans, other mammals, and birds.
Retroviral integrase (IN) is an enzyme produced by a retrovirus that integrates its genetic information into that of the host cell it infects. Retroviral INs are not to be confused with phage integrases (recombinases) used in biotechnology, such as λ phage integrase, as discussed in site-specific recombination.
A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.
Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials, a larger group which also includes antibiotic, antifungal and antiparasitic drugs, or antiviral drugs based on monoclonal antibodies. Most antivirals are considered relatively harmless to the host, and therefore can be used to treat infections. They should be distinguished from virucides, which are not medication but deactivate or destroy virus particles, either inside or outside the body. Natural virucides are produced by some plants such as eucalyptus and Australian tea trees.
An HIV vaccine is a potential vaccine that could be either a preventive vaccine or a therapeutic vaccine, which means it would either protect individuals from being infected with HIV or treat HIV-infected individuals.
Adenoviruses are medium-sized, nonenveloped viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953.
Tripartite motif-containing protein 5 also known as RING finger protein 88 is a protein that in humans is encoded by the TRIM5 gene. The alpha isoform of this protein, TRIM5α, is a retrovirus restriction factor, which mediates a species-specific early block to retrovirus infection.
Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure. Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs. Both in-vivo assembly and in-vitro assembly have been successfully shown to form virus-like particles. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera. VLPs have been produced from components of a wide variety of virus families including Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages. VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells.
In molecular biology, CD4 is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984. In humans, the CD4 protein is encoded by the CD4 gene.
The genome and proteins of HIV (human immunodeficiency virus) have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.
Envelope glycoprotein GP120 is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1984. The 120 in its name comes from its molecular weight of 120 kDa. Gp120 is essential for virus entry into cells as it plays a vital role in attachment to specific cell surface receptors. These receptors are DC-SIGN, Heparan Sulfate Proteoglycan and a specific interaction with the CD4 receptor, particularly on helper T-cells. Binding to CD4 induces the start of a cascade of conformational changes in gp120 and gp41 that lead to the fusion of the viral membrane with the host cell membrane. Binding to CD4 is mainly electrostatic although there are van der Waals interactions and hydrogen bonds.
Herpes simplex virus1 and 2, also known by their taxonomic names Human alphaherpesvirus 1 and Human alphaherpesvirus 2, are two members of the human Herpesviridae family, a set of viruses that produce viral infections in the majority of humans. Both HSV-1 and HSV-2 are very common and contagious. They can be spread when an infected person begins shedding the virus.
APOBEC3G is a human enzyme encoded by the APOBEC3G gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important role in innate anti-viral immunity. APOBEC3G belongs to the family of cytidine deaminases that catalyze the deamination of cytidine to uridine in the single stranded DNA substrate. The C-terminal domain of A3G renders catalytic activity, several NMR and crystal structures explain the substrate specificity and catalytic activity.
Simian foamy virus (SFV) is a species of the genus Spumavirus that belongs to the family of Retroviridae. It has been identified in a wide variety of primates, including prosimians, New World and Old World monkeys, as well as apes, and each species has been shown to harbor a unique (species-specific) strain of SFV, including African green monkeys, baboons, macaques, and chimpanzees. As it is related to the more well-known retrovirus human immunodeficiency virus (HIV), its discovery in primates has led to some speculation that HIV may have been spread to the human species in Africa through contact with blood from apes, monkeys, and other primates, most likely through bushmeat-hunting practices.
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