Synergistic Effect by Combining a gp120-Binding Protein and a gp41-Binding Antibody to Inactivate HIV-1 Virions and Inhibit HIV-1 Infection
Abstract
:1. Introduction
2. Results
2.1. Combinatorial Use of mD1.22 and D5 scFv Exhibited Strong Synergism in Inhibiting Infection of HIV-1 Laboratory Strains
2.2. Combinatorial Use of mD1.22 and D5 scFv Exhibited Synergism in Inhibiting Infection by Divergent HIV-1 Strains
2.3. D5 scFv Enhances mD1.22-Mediated Inactivating Effect on HIV-1 Laboratory Strains and Primary HIV-1 Isolates
2.4. D5 scFv Enhances mD1.22-Mediated Inactivation Against T20-Resistant HIV-1 Strains and AZT-Resistant HIV-1 Strains
2.5. D5 scFv Enhances the Inactivation Activity of mD1.22 against the LRA-Reactivated HIV-1 Virions
3. Discussion
4. Materials and Methods
4.1. Cells, Virus and Proteins
4.2. Inactivation of HIV-1 Virions
4.3. Inhibition of HIV-1 Infection
4.4. Detecting the Ability of mD1.22 to Inactivate LRA-Reactivated HIV-1 Virions Released from ACH-2 Cells
4.5. Combination Index (CI)
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
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Virus Strain | CI | mD1.22 | D5 scFv | ||||
---|---|---|---|---|---|---|---|
IC50 (nM) | Fold of Enhancement | IC50 (nM) | Fold of Enhancement | ||||
Alone | In Combination | Alone | In Combination | ||||
HIV-1 Laboratory Strains | |||||||
IIIB (X4) | 0.16 | 16.57 | 1.23 | 12.47 | 518.03 | 42.97 | 11.06 |
Bal (R5) | 0.57 | 13.49 | 3.59 | 2.76 | 1190.51 | 359.11 | 2.32 |
HIV-1 Primary Isolates | |||||||
91US_4 | 0.59 | 26.88 | 7.87 | 2.42 | 674.25 | 196.81 | 2.43 |
92UG024 | 0.38 | 7.58 | 0.32 | 22.69 | 318.82 | 108.01 | 1.95 |
NP1525 | 0.20 | 22.97 | 2.66 | 7.64 | 3070.19 | 265.68 | 10.56 |
T20-Resistant HIV-1 Strains | |||||||
HIV-1 NL4-3 D36G (WT) | 0.47 | 14.00 | 2.71 | 4.17 | 386.82 | 108.42 | 2.57 |
(D36G) N42T, N43K | 0.79 | 14.58 | 5.72 | 1.55 | 286.19 | 114.47 | 1.50 |
(D36G) V38A, N42T | 0.64 | 12.69 | 4.20 | 2.02 | 345.41 | 105.01 | 2.29 |
AZT-Resistant HIV-1 Strains | |||||||
629 | 0.79 | 17.34 | 6.44 | 1.69 | 764.82 | 322.18 | 1.37 |
964 | 0.24 | 7.19 | 0.90 | 6.99 | 389.64 | 45.03 | 7.65 |
Virus Strains | Concentration (nM) of mD1.22 | Fold of Enhancement | ||
---|---|---|---|---|
Alone | In Combination | |||
HIV-1 Laboratory-Adapted Strains | ||||
IIIB (X4) | EC50 | 2.09 | 0.64 | 2.27 |
EC90 | 11.54 | 1.21 | 8.54 | |
Bal (R5) | EC50 | 9.12 | 1.75 | 4.21 |
EC90 | 17.46 | 4.68 | 2.73 | |
Primary HIV-1 Isolates | ||||
91US_4 | EC50 | 4.28 | 1.99 | 1.15 |
EC90 | 8.51 | 3.80 | 1.24 | |
97TH_NP1525 | EC50 | 5.92 | 2.51 | 1.36 |
EC90 | 31.23 | 15.74 | 0.98 | |
92UG024 | EC50 | 13.43 | 2.20 | 5.10 |
EC90 | 41.49 | 12.09 | 2.43 | |
T20-Resistant HIV-1 Strains | ||||
HIV-1 NL4-1 D36G (WT) | EC50 | 1.10 | 0.66 | 0.67 |
EC90 | 2.12 | 1.16 | 0.83 | |
(D36G) N42T, N43K | EC50 | 2.56 | 0.58 | 3.41 |
EC90 | 3.82 | 1.24 | 2.08 | |
(D36G) V38A, N42T | EC50 | 5.08 | 2.49 | 1.04 |
EC90 | 10.03 | 6.28 | 0.60 | |
AZT- Resistant HIV-1 Strains | ||||
629 | EC50 | 11.28 | 4.78 | 1.36 |
EC90 | 20.08 | 8.84 | 1.27 | |
964 | EC50 | 3.19 | 1.56 | 1.04 |
EC90 | 23.80 | 3.23 | 6.37 |
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Wang, X.; Cao, M.; Wu, Y.; Xu, W.; Wang, Q.; Ying, T.; Lu, L.; Jiang, S. Synergistic Effect by Combining a gp120-Binding Protein and a gp41-Binding Antibody to Inactivate HIV-1 Virions and Inhibit HIV-1 Infection. Molecules 2021, 26, 1964. https://doi.org/10.3390/molecules26071964
Wang X, Cao M, Wu Y, Xu W, Wang Q, Ying T, Lu L, Jiang S. Synergistic Effect by Combining a gp120-Binding Protein and a gp41-Binding Antibody to Inactivate HIV-1 Virions and Inhibit HIV-1 Infection. Molecules. 2021; 26(7):1964. https://doi.org/10.3390/molecules26071964
Chicago/Turabian StyleWang, Xinling, Miao Cao, Yanling Wu, Wei Xu, Qian Wang, Tianlei Ying, Lu Lu, and Shibo Jiang. 2021. "Synergistic Effect by Combining a gp120-Binding Protein and a gp41-Binding Antibody to Inactivate HIV-1 Virions and Inhibit HIV-1 Infection" Molecules 26, no. 7: 1964. https://doi.org/10.3390/molecules26071964