Defective proviruses rapidly accumulate during acute HIV-1 infection
| Autor: | Bruner, Katherine M, Murray, Alexandra J, Pollack, Ross A, Soliman, Mary G, Laskey, Sarah B, Capoferri, Adam A, Lai, Jun, Strain, Matthew C, Lada, Steven M, Hoh, Rebecca, Ho, Ya-Chi, Richman, Douglas D, Deeks, Steven G, Siliciano, Janet D, Siliciano, Robert F |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adult Male Anti-HIV Agents Immunology HIV Infections Virus Replication Polymerase Chain Reaction Medical and Health Sciences Cohort Studies Young Adult Proviruses 2.2 Factors relating to the physical environment 2.1 Biological and endogenous factors Humans Aged Bayes Theorem Viral Load Middle Aged Virus Latency Infectious Diseases Acute Disease HIV-1 Disease Progression HIV/AIDS Female Infection |
| Zdroj: | Bruner, Katherine M; Murray, Alexandra J; Pollack, Ross A; Soliman, Mary G; Laskey, Sarah B; Capoferri, Adam A; et al.(2016). Defective proviruses rapidly accumulate during acute HIV-1 infection.. Nature medicine, 22(9), 1043-1049. doi: 10.1038/nm.4156. UC Office of the President: Research Grants Program Office (RGPO). Retrieved from: http://www.escholarship.org/uc/item/78h9x20k Nature medicine, vol 22, iss 9 |
| DOI: | 10.1038/nm.4156. |
| Popis: | Although antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, human immunodeficiency virus type 1 (HIV-1) persists in CD4(+) T cells in a latent form that is not targeted by the immune system or by ART. This latent reservoir is a major barrier to curing individuals of HIV-1 infection. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective. However, the dynamics of the accumulation and the persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. By using an unbiased method to amplify near-full-length proviral genomes from HIV-1-infected adults treated at different stages of infection, we demonstrate that early initiation of ART limits the size of the reservoir but does not profoundly affect the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals who were treated early versus late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size, as determined by the number of genetically intact proviruses. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies. |
| Databáze: | OpenAIRE |
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