Title: Entry Inhibitors of Human Immunodeficiency Virus
Abstract: Highly active antiretroviral therapy (HAART) based on the combination of different classes of inhibitors has dramatically improved the prognosis of human immunodeficiency virus type 1 (HIV-1) infection after its establishment. This chapter focuses on the viral entry processes that play crucial roles in HIV-1 replication and describes inhibitors thereof. It talks about three kinds of inhibitor named as fusion inhibitors, coreceptor inhibitors and viral attachment inhibitors. Maraviroc was approved for use in combination with other antiretroviral medications for the treatment of R5 HIV-1 in adults whose viral loads remain detectable despite existing antiretroviral treatment or who have multidrug-resistant HIV-1. HIV-1 variants resistant to Cyanovirin-N (CV-N) or cross-resistant to additional carbohydrate-binding agents were generated and examined for their biological properties. A study on resistance to CV-N demonstrated that the resistant variants had increased susceptibility to immunoglobulins and sera obtained from HIV-1-infected patients and particularly to V3-loop-directed monoclonal antibodies. The maraviroc-resistant R5 HIV-1 retained full susceptibility to SCH-C and aplaviroc, suggesting that although the CCR5 binding sites for these agents are similar, their impacts on the surface conformation of the receptor are different. The results of the study also suggest that the envelope proteins of maraviroc-resistant viruses are able to recognize and utilize inhibitor-bound CCR5, which involves the ordered accumulation of mutations in the viral envelope, both in the V3 loop and elsewhere within gp120. In addition to the inhibitors described in the chapter, several antibodies have been shown to interact with the molecules essential for HIV-1 entry to the host cells.
Publication Year: 2014
Publication Date: 2014-04-30
Language: en
Type: book-chapter
Indexed In: ['crossref']
Access and Citation
AI Researcher Chatbot
Get quick answers to your questions about the article from our AI researcher chatbot