Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants and Sample Collection
2.2. Laboratory Methods
2.2.1. Single-Genome Amplification and Sequencing of HIV-1 Viruses
2.2.2. Targeted Genome Region Next-Generation Sequencing
2.3. Data Analysis
2.3.1. Single-Genome Amplification-Derived Sequence Analysis
2.3.2. Next-Generation Sequencing Data Analysis
3. Results
3.1. Study Participants
3.2. Single-Genome Amplification and Sequencing Analysis
3.3. Next-Generation Sequencing
3.4. Participant 2547279
3.5. Participant 2546340
3.6. Participant 2549813
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Disclaimer
References
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Participant ID | Sex/Age (Years) | Transmitted/Founder (T/F) Infection | Subtype | Fiebig Stage 1 | CD4 Cells/mL | Plasma HIV RNA log10 Copies/mL | CSF HIV RNA log10 Copies/mL | CSF WBC Cells/mL | Sample Time (Estimated Days Post Infection) | Number of Sequences (Plasma:CSF) | Env Genetic Diversity | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean (SD) | P-Value 2 | ||||||||||||||
Plasma | CSF | Intra Plasma | Intra CSF | Inter Plasma/CSF | Intra Plasma vs. Intra CSF | ||||||||||
2545573 | M/28 | Single | CRF01_AE | II | 426 | 6.50 | 4.13 | 10 | 14 | 15 | 26:23 | 0.062% (0.054%) | 0.071% (0.053%) | 0.066% (0.055%) | 0.001 |
2546083 | F/29 | Single | CRF01_AE | IV | 463 | 5.76 | 4.64 | 50 | 32 | 35 | 12:10 | 0.026% (0.033%) | 0.047% (0.048%) | 0.036% (0.043%) | 0.026 |
2549583 | M/30 | Single | CRF01_AE | III | 293 | 5.59 | 5.39 | 0 | 26 | 27 | 23:23 | 0.03% (0.03%) | 0.023% (0.033%) | 0.027% (0.032%) | 0.002 |
2543832 | M/36 | Single | CRF01_AE | II | 269 | 7.56 | 4.07 | 0 | 18 | 27 | 11:10 | 0.021% (0.032%) | 0.023% (0.024%) | 0.022% (0.03%) | 0.25 |
2545436 | M/32 | Single | CRF01_AE | III | 621 | 7.49 | 4.04 | 160 | 16 | 19 | 10:11 | 0.047% (0.035%) | 0.062% (0.046%) | 0.054% (0.042%) | 0.22 |
2543625 | M/21 | Multiple | CRF01_AE | III | 181 | 5.52 | 5.41 | 110 | 22 | 27 | 10:10 | 0.42% (0.615%) | 0.079 % (0.079%) | 0.252% (0.46%) | <0.0001 |
2543733 | M/30 | Single | CRF01_AE | II | 569 | 5.07 | 4.64 | 4 | 15 | 16 | 24:24 | 0.01% (0.018%) | 0.055% (0.045%) | 0.033% (0.035%) | <0.0001 |
2549844 | M/24 | Single | CRF01_AE | V | 231 | 6.12 | 5.20 | 7 | 16 | 19 | 10:10 | 0.063% (0.04%) | 0.102% (0.067%) | 0.082% (0.058%) | 0.013 |
2546609 | M/29 | Multiple | CRF01_AE | III | 206 | 6.61 | 4.41 | 3 | 28 | 29 | 29:29 | 1.897% (3.811%) | 0.674% (2.131%) | 1.286% (3.157%) | <0.0001 |
2546340 | M/29 | Multiple | CRF01_AE | IV | 338 | 7.37 | 5.55 | 0 | 23 | 24 | 27:43 | 1.315% (3.175%) | 0.191% (0.188%) | 0.773% (2.366%) | 0.0002 |
2548123 | F/45 | Single | CRF01_AE | III | 132 | 7.41 | 5.3 | 0 | 22 | 23 | 10:NA | 0.054% (0.033%) | NA | NA | NA |
2547279 | M/27 | Multiple | CRF01_AE | IV | 234 | 6.86 | 5.08 | 0 | 28 | 28 | 11:NA | 0.221% (0.259%) | NA | NA | NA |
2545383 | M/37 | Multiple | CRF01_AE | III | 252 | 7.41 | 5.54 | 0 | 20 | 20 | 10:NA | 0.301% (0.497%) | NA | NA | NA |
2548105 | M/40 | Multiple | CRF01_AE | V | 374 | 5.84 | 4.07 | 0 | 25 | 26 | 10:NA | 2.317% (2.121%) | NA | NA | NA |
2549813 | M/22 | Multiple | CRF01_AE | II | 165 | 6.71 | 6.61 | 0 | 19 | 20 | 10:NA | 0.374% (0.620%) | NA | NA | NA |
2547268 | M/23 | Multiple | CRF01_AE | III | 334 | 6.95 | 5.22 | 0 | 32 | 33 | 10:NA | 1.263% (2.093%) | NA | NA | NA |
2544636 | M/29 | Single | B/CRF01_AE | II | 453 | 5.41 | 5.17 | 0 | 25 | 25 | 8:NA | 0.000% (0.000%) | NA | NA | NA |
2548522 | M/29 | Single | CRF01_AE | III | 265 | 7.75 | 4.22 | 0 | 17 | 18 | 10:NA | 0.024% (0.024%) | NA | NA | NA |
Compartmentalization of Variant Sequences (Ratio of Variants in Plasma:CSF > 1.5) * | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
pol protease | pol reverse transcriptase | env | ||||||||||||||||||
POL PR I | POL PR II | POL PR III | POL RT I | POL RT II | POL RT III | ENV V2 | ||||||||||||||
Participant ID | Major | Minor | Major | Minor | Major | Minor | Major | Minor | Major | Minor | Major | Minor | Major | Minor | ||||||
2546609 | No | - | - | - | - | - | No | - | No | - | No | - | No | - | ||||||
2547279† | No | No | - | - | - | - | No | No | No | No | - | - | No | Yes | ||||||
2543625† | No | Yes | No | Yes | - | - | - | - | - | - | - | - | No | No | ||||||
2545383† | - | - | - | - | - | - | No | Yes | No | Yes | - | - | No | Yes | ||||||
2546340 | No | No | No | Yes | No | Yes | No | Yes | No | Yes | No | Yes | No | No | ||||||
2548105† | No | Yes | No | Yes | No | Yes | No | Yes | No | Yes | No | Yes | No | Yes | ||||||
2547268† | No | Yes | No | Yes | - | - | No | Yes | No | Yes | - | - | No | Yes | ||||||
2549813 | Yes | Yes | Yes | Yes | - | - | Yes | Yes | Yes | Yes | Yes | Yes | Yes | Yes |
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Share and Cite
Tovanabutra, S.; Sirijatuphat, R.; Pham, P.T.; Bonar, L.; Harbolick, E.A.; Bose, M.; Song, H.; Chang, D.; Oropeza, C.; O’Sullivan, A.M.; et al. Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection. Cells 2019, 8, 902. https://doi.org/10.3390/cells8080902
Tovanabutra S, Sirijatuphat R, Pham PT, Bonar L, Harbolick EA, Bose M, Song H, Chang D, Oropeza C, O’Sullivan AM, et al. Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection. Cells. 2019; 8(8):902. https://doi.org/10.3390/cells8080902
Chicago/Turabian StyleTovanabutra, Sodsai, Rujipas Sirijatuphat, Phuc T. Pham, Lydia Bonar, Elizabeth A. Harbolick, Meera Bose, Hongshuo Song, David Chang, Celina Oropeza, Anne Marie O’Sullivan, and et al. 2019. "Deep Sequencing Reveals Central Nervous System Compartmentalization in Multiple Transmitted/Founder Virus Acute HIV-1 Infection" Cells 8, no. 8: 902. https://doi.org/10.3390/cells8080902