The role of lysine residue at amino acid position 165 of human immunodeficiency virus type 1 CRF01_AE Gag in reducing viral drug susceptibility to protease inhibitors
| Autor: | Shota Nakamura, Kazuyoshi Ikuta, Masanori Kameoka, Pathom Sawanpanyalert, Wattana Auwanit, Kenzo Tokunaga, Panasda Isarangkura-na-ayuthaya, Sompong Sapsutthipas, Yoko Kameoka, Bongkot Soonthornsata |
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| Rok vydání: | 2010 |
| Předmět: |
Gene Expression Regulation
Viral Anti-HIV Agents viruses medicine.medical_treatment Molecular Sequence Data Lysine Biology Recombinant virus gag Gene Products Human Immunodeficiency Virus Cell Line law.invention Drug Resistance Multiple Viral immune system diseases law Virology medicine Humans Protease Inhibitors CRF01_AE Amino Acid Sequence Peptide sequence Subtypes chemistry.chemical_classification Protease virus diseases biochemical phenomena metabolism and nutrition Recombinant Proteins Amino acid Protease inhibitor chemistry Virion assembly Cell culture Drug resistance HIV-1 Recombinant DNA Gag p24 |
| Zdroj: | Virology. 405(1):129-138 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2010.06.003 |
| Popis: | Recombinant human immunodeficiency virus type 1 (HIV-1) containing a CRF01_AE Gag, AE-Gag62, was significantly less susceptible to protease inhibitors (PIs) than the subtype B reference strain, NL4-3; therefore, the mechanism of how AE-Gag62 reduced viral drug susceptibility to PIs was studied in this report. The results showed that the lysine residue at amino acid position 165 (K165) of AE-Gag62 played a role in reducing the drug susceptibility of the recombinant virus to PIs. In addition, K165 potentially appears more frequently in CRF01_AE viruses than in the viruses of other major HIV-1 subtypes. Although K165 had no effect on the extent of recombinant protease-mediated in vitro Gag cleavage, it enhanced the incorporation of the Gag–Pol precursor protein, p160, into virions. Taken together, these results suggest that K165 of CRF01_AE Gag affects the regulation of virion assembly or maturation, and reduces viral drug susceptibility to PIs. |
| Databáze: | OpenAIRE |
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