HIV-1 Gag-Pol Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Subjects
2.2. Amplification and Sequencing Of Transmitted Virus for Identification of Early Gag-Pol Sequences
2.3. Generation of Gag-Pol-NL4.3 Chimera Infectious Clones
2.4. In Vitro Assay for HIV-1 Replicative Capacity
2.5. Quantification of HIV-1 Reverse Transcriptase Using Radioactive and Colorimetric Assays
2.6. Protein Domain Methods
2.7. Additional
3. Results
3.1. Participant and Virus Characteristics
3.2. Gag-Pol-NL4.3 Chimeras Showed a Range of Replicative Capacities
3.3. There Was No Difference in Set Point Viral Load, CD4+ T Cell Count Decline and Subtypes
3.4. Protein Domain Diversity of Gag-Pol Regions
3.5. Variation of Gag-Pol Domains Linked to Elevated VRC
3.6. Protein Changes in Gag-P6 Region
3.7. Global Gag-P6 Domain Variation
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Participant ID | Subtype a | VRC Score | Participant Gender | Participant Age | Days Post-EDI | Set Point Viral Load | Visit CD4 Count (Cells/µL) |
---|---|---|---|---|---|---|---|
191084 | A1 | 0.21 | Female | 29 | 27 | 61,309 | 777 |
191637 | A1 | 0.18 | Male | 31 | 85 | 26,595 | 634 |
191734 | A1 | 0.35 | Male | 44 | 67 | 38,081 | 462 |
191918 | A1 | 0.11 | Male | 22 | 56 | 8005 | 878 |
194180 | A1 | 0.3 | Male | 46 | 59 | 37,767 | 438 |
270909 | A1 | 0.22 | Male | 41 | 50 | 189,054 | 536 |
Mean * | -- | -- | -- | 35.5 | 57.33 | 60,135 | 621 |
191996 | D | 0.53 | Female | 37 | 55 | 1599 | 806 |
192002 | D | 0.37 | Female | 27 | 50 | 2122 | 569 |
194020 | D | 0.55 | Male | 33 | 36 | ND | 783 |
194037 | D | 0.55 | Male | 34 | 51 | 33,550 | 531 |
194374 | D | 0.43 | Male | 33 | 35 | 31,954 | 401 |
194535 | D | 0.48 | Male | 39 | 47 | ND | 281 |
194603 | D | 0.58 | Female | 33 | 52 | ND | 887 |
194604 | D | 0.53 | Female | 35 | 44 | 69,512 | 677 |
270015 | D | 0.15 | Male | 58 | 11 | 14,064 | 355 |
270535 | D | 0.07 | Male | 31 | 73 | 5197 | 796 |
275026 | D | 0.46 | Female | 21 | 51 | 96,368 | 277 |
275031 | D | 0.44 | Male | 31 | 25 | 4260 | 795 |
194065 | D | 0.58 | Male | 41 | 42 | 20,890 | 470 |
Mean ** | -- | -- | -- | 34.85 | 44 | 27,952 | 587 |
193008 | A1D | 1.34 | Male | 27 | 23 | 57,464 | 798 |
191639 | A1D | 0.47 | Male | 50 | 50 | 117,145 | 1149 |
191696 | A1D | 0.33 | Male | 29 | 50 | 239,477 | 398 |
191735 | A1D | 0.38 | Male | 22 | 56 | 2482 | 754 |
191923 | A1D | 1.11 | Female | 31 | 55 | 28,929 | 242 |
191955 | A1D | 0.76 | Female | 39 | 23 | 696 | 997 |
191997 | A1D | 0.97 | Male | 31 | 57 | 1002 | 764 |
194346 | A1D | 0.75 | Male | 29 | 31 | 415,426 | 346 |
194584 | A1D | 0.43 | Female | 33 | 25 | 7780 | 580 |
275027 | A1D | 0.73 | Female | 22 | 61 | 163,395 | 651 |
192018 | A1C | 0.96 | Male | 22 | 29 | 24,769 | 352 |
193006 | CD | 1.16 | Male | 24 | 52 | 47,355 | 478 |
270475 | 01AE | 1.13 | Female | 28 | 43 | 14,528 | 531 |
Mean *** | -- | -- | -- | 29.77 | 42.69 | 86,188 | 618 |
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Kapaata, A.; Balinda, S.N.; Xu, R.; Salazar, M.G.; Herard, K.; Brooks, K.; Laban, K.; Hare, J.; Dilernia, D.; Kamali, A.; et al. HIV-1 Gag-Pol Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity. Viruses 2021, 13, 171. https://doi.org/10.3390/v13020171
Kapaata A, Balinda SN, Xu R, Salazar MG, Herard K, Brooks K, Laban K, Hare J, Dilernia D, Kamali A, et al. HIV-1 Gag-Pol Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity. Viruses. 2021; 13(2):171. https://doi.org/10.3390/v13020171
Chicago/Turabian StyleKapaata, Anne, Sheila N. Balinda, Rui Xu, Maria G. Salazar, Kimberly Herard, Kelsie Brooks, Kato Laban, Jonathan Hare, Dario Dilernia, Anatoli Kamali, and et al. 2021. "HIV-1 Gag-Pol Sequences from Ugandan Early Infections Reveal Sequence Variants Associated with Elevated Replication Capacity" Viruses 13, no. 2: 171. https://doi.org/10.3390/v13020171