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High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men
Open accessAbstract
Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5' and 3' half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3-6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized.
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DnaSP, DNA polymorphism analyses by the coalescent and other methods
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Yang, R., Sun, L., Li, C.-F., Wang, Y.-H., Yao, J., Li, H., Yan, M., Chang, W.-C., Hsu, J.-M., Cha, J.-H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21099-2 · Cited by 632
Self-citationPhenotypic properties of transmitted founder HIV-1
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Metadata
- Authors
- Li, H., Bar, K. J., Wang, S., Decker, J. M., Chen, Y., Sun, C., Salazar-Gonzalez, J. F., Salazar, M. G., Learn, G. H., Morgan, C. J., Schumacher, J. E., Hraber, P., Giorgi, E. E., Bhattacharya, T., Korber, B. T., Perelson, A. S., Eron, J. J., Cohen, M. S., Hicks, C. B., Haynes, B. F., Markowitz, M., Keele, B. F., Hahn, B. H., & Shaw, G. M.
- Venue
- PLoS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-05-13
- Volume
- 6
- Issue
- 5
- Pages
- e1000890
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- OpenAlex
- W1963704583
- Cited by
- 297
- References
- 55
- FWCI
- 11.68
- Type
- journal article
- Language
- en
- Open access
- gold
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- Li, H., Bar, K. J., Wang, S., Decker, J. M., Chen, Y., Sun, C., Salazar-Gonzalez, J. F., Salazar, M. G., Learn, G. H., Morgan, C. J., Schumacher, J. E., Hraber, P., Giorgi, E. E., Bhattacharya, T., Korber, B. T., Perelson, A. S., Eron, J. J., Cohen, M. S., Hicks, C. B., . . . Shaw, G. M. (2010). High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1000890
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