Title : HIV-1 and its resistance to peptidic carbohydrate-binding agents (CBAs): an overview
Abstract :
- The glycoproteins on the surfaces of enveloped viruses, such as HIV, can be considered as a unique target for antiviral therapy
- Different carbohydrate-binding agents (CBAs) target specific glycans present on viral glycoproteins of enveloped viruses
- It has been shown that long-term CBA pressure in vitro can result in mutant HIV-1 isolates with several N-linked glycan deletions on gp120
- These studies demonstrated that mainly high-mannose type glycans are deleted
- However, interestingly, N241, N262 and N356 on gp120 have never been found to be affected after prolonged CBA exposure
- Here, we review the mutation and (cross)-resistance profiles of eleven specific generated CBA-resistant HIV-1 strains
- We observed that the broad-neutralizing anti-carbohydrate binding mAb 2G12 became completely inactive against all the generated CBA-resistant HIV-1 clade B isolates
- In addition, all of the CBAs discussed in this review, with the exception of NICTABA, interfered with the binding of 2G12 mAb to gp120 expressed on HIV-1-infected T cells
- The cross-resistance profiles of mutant HIV-1 strains are varying from increased susceptibility to very high resistance levels, even among different classes of CBAs with dissimilar sugar specificities or binding moieties [e.g., α (1,3 ), α (1,2 ), α (1,6 )]
- Recent studies demonstrated promising results in non-topical formulations (e.g., intranasally or subcutaneously), highlighting their potential for prevention (microbicides) and antiviral therapy
Output (sent_index, trigger,
protein,
sugar,
site):
- 1. glycoproteins, , glycoproteins, -, -
- 2. glycoproteins, , glycoproteins, -, -
- 2. present, , glycoproteins, specific glycans, -
- 3. deletions, , gp120, deletions, -
Output(Part-Of) (sent_index,
protein,
site):
- 5. gp120, N241, N262 and N356
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):