HIV Related Peptides
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Introduction
HIV is divided into two subtypes, HIV-1 and HIV-2, and the majority of AIDS patients in the world are infected by HIV-1. HIV-1 is an RNA virus whose genome is composed of about 9,200bp. Its genome encodes three major structural peptides Gag, Pol and Env, two regulatory peptides Tat and Rev, and four auxiliary peptides Nef, Vpr, Vif and Vpu. Besides, HIV-1 related peptides also include nucleocapsid peptides NCp7, GP120, GP41 and so on. At present, the drug designs for these peptides has become one of the hot topics in AIDS research.
Mechanism of action
This article selects several important HIV related peptides to explain their respective significance for the existence, replication and infection of HIV-1. Gag, a structural protein, facilitates protein-albumin interactions, protein-RNA interactions, and protein-lipid interactions by synergizing its own different regions, thus promoting the production of mature infective virus particles. For another, Tat in cells participates in HIV transcriptional activation and promotes HIV replication, meanwhile, extracellular Tat promotes the occurrence and the development of AIDS. Moreover, Rev is able to accelerate transporting the mRNA to the outside of nucleus. When the Rev lacks or cannot enter the nucleus, mRNA unspliced or partially spliced will be completely degraded, resulting in the interruption of HIV-1 replication. The main function of Vif peptides is to mediate apolipoprotein B mRNA editing enzyme in host’s cell to catalyze the degration of polypeptide like 3G to increase the infectivity of the virus.
Application of HIV Related Peptides
Because these HIV related peptides play such important roles in the development of HIV virus, the inhibitors designed according to the function of them may become one of the main drugs to treat AIDS. Aiming at the Gag, scientists have produced a variety of HIV inhibitors, including assembly inhibitor such as CAP, budding release inhibitors such as hydrazone and hydrazide peptides, and maturation inhibitor, for example, UK-201844. There also are various inhibitors of ADIS are designed according to the Tat, they are focused on the four types, and they are the intracellular antibodies, the Tat vaccine, the antitat antibody drugs, and the nonprotein drugs. For the time being, Vif related inhibitors can be divided into the following two categories: inhibitors that up-regulate intracellular APOBEC3G level, Inhibitors that down-regulate Vif protein levels.
References
- Harris RS, Liddament MT. (2004). Retroviral restriction by APOBEC proteins. Nat Rev Immuno, 4, 868-877.
- Carr JM, Coolen C, Davis AJ, et al. (2008). Human immunodeficiency virus 1 (HIV-1) virion infectivity factor (Vif) is part of reverse transcription complexes and acts as an accessory factor for reverse transcription. Virology, 372, 147-156.
