Transcriptional signature of resting-memory CD4 T cells differentiates spontaneous from treatment-induced HIV control
Por:
Garcia, M, Lopez-Fernandez, L, Minguez, P, Moron-Lopez, S, Restrepo, C, Navarrete-Munoz, MA, Lopez-Bernaldo, JC, Benguria, A, Garcia, MI, Cabello, A, Fernandez-Guerrero, M, De la Hera, FJ, Estrada, V, Barros, C, Martinez-Picado, J, Gorgolas, M, Benito, JM and Rallon, N
Publicada:
1 ago 2020
Ahead of Print:
1 jun 2020
Resumen:
The HIV reservoir is the main barrier to eradicating HIV infection, and resting memory CD4 T (Trm) cells are one of the most relevant cellular component harboring latent proviruses. This is the first study analyzing the transcriptional profile of Trm cells, in two well-characterized groups of HIV patients with distinct mechanisms of viral replication control (spontaneous versus treatment-induced). We use a systems biology approach to unravel subtle but important differences in the molecular mechanisms operating at the cellular level that could be associated with the host's ability to control virus replication and persistence. Despite the absence of significant differences in the transcriptome of Trm cells between Elite Controllers (ECs) and cART-treated (TX) patients at the single gene level, we found 353 gene ontology (GO) categories upregulated in EC compared with TX. Our results suggest the existence of mechanisms at two different levels: first boosting both adaptive and innate immune responses, and second promoting active viral replication and halting HIV latency in the Trm cell compartment of ECs as compared with TX patients. These differences in the transcriptional profile of Trm cells could be involved in the lower HIV reservoir observed in ECs compared with TX individuals, although mechanistic studies are needed to confirm this hypothesis. Combining transcriptome analysis and systems biology methods is likely to provide important findings to help us in the design of therapeutic strategies aimed at purging the HIV reservoir. Key messages
HIV-elite controllers have the lowest HIV-DNA content in resting memory CD4 T cells. HIV-ECs show a particular transcriptional profile in resting memory CD4 T cells. Molecular mechanisms of enhanced adaptative and innate immune response in HIV-ECs. High viral replication and low viral latency establishment associate to the EC status.
Filiaciones:
Garcia, M:
UAM, HIV & Viral Hepatitis Res Lab, Inst Invest Sanitaria Fdn Jimenez Diaz, Univ Autonoma Madrid IIS FJD, Ave Reyes Catolicos 2, Madrid 28040, Spain
Hosp Univ Rey Juan Carlos, Mostoles, Spain
Hosp Gen Univ Gregorio Maranon, Dept Pharm, Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain
Lopez-Fernandez, L:
Hosp Gen Univ Gregorio Maranon, Dept Pharm, Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain
Minguez, P:
Inst Invest Sanitaria Fdn Jimenez Diaz IIS FJD, Bioinformat Unit, Dept Genet, Madrid, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Restrepo, C:
UAM, HIV & Viral Hepatitis Res Lab, Inst Invest Sanitaria Fdn Jimenez Diaz, Univ Autonoma Madrid IIS FJD, Ave Reyes Catolicos 2, Madrid 28040, Spain
Hosp Univ Rey Juan Carlos, Mostoles, Spain
Navarrete-Munoz, MA:
UAM, HIV & Viral Hepatitis Res Lab, Inst Invest Sanitaria Fdn Jimenez Diaz, Univ Autonoma Madrid IIS FJD, Ave Reyes Catolicos 2, Madrid 28040, Spain
Hosp Univ Rey Juan Carlos, Mostoles, Spain
Lopez-Bernaldo, JC:
Hosp Gen Univ Gregorio Maranon, Madrid, Spain
Benguria, A:
Ctr Nacl Invest Cardiovasc CNIC, Genom Unit, Madrid, Spain
Garcia, MI:
Hosp Gen Univ Gregorio Maranon, Dept Pharm, Inst Invest Sanitaria Gregorio Maranon, Madrid, Spain
Cabello, A:
Hosp Univ Fdn Jimenez Diaz, Madrid, Spain
Fernandez-Guerrero, M:
Hosp Univ Fdn Jimenez Diaz, Madrid, Spain
De la Hera, FJ:
Hosp Univ Fdn Jimenez Diaz, Madrid, Spain
Estrada, V:
Hosp Univ Clin San Carlos, Madrid, Spain
Barros, C:
Hosp Univ Mostoles, Mostoles, Spain
:
irsiCaixa AIDS Res Inst, Badalona, Spain
Univ Vic Cent Univ Catalonia UVic UCC, Vic, Spain
Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain
Gorgolas, M:
Hosp Univ Fdn Jimenez Diaz, Madrid, Spain
Benito, JM:
UAM, HIV & Viral Hepatitis Res Lab, Inst Invest Sanitaria Fdn Jimenez Diaz, Univ Autonoma Madrid IIS FJD, Ave Reyes Catolicos 2, Madrid 28040, Spain
Hosp Univ Rey Juan Carlos, Mostoles, Spain
Rallon, N:
UAM, HIV & Viral Hepatitis Res Lab, Inst Invest Sanitaria Fdn Jimenez Diaz, Univ Autonoma Madrid IIS FJD, Ave Reyes Catolicos 2, Madrid 28040, Spain
Hosp Univ Rey Juan Carlos, Mostoles, Spain
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