ZBTB gene expression in HIV patients: a possible new molecular mechanism of viral control
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ORIGINAL ARTICLE
ZBTB gene expression in HIV patients: a possible new molecular mechanism of viral control Judith Carolina De Arcos‑Jiménez1,2 · Luz Alicia González‑Hernández2,3 · Sarah Ratkovich‑González1,2 · Karina Sánchez‑Reyes2 · Monserrat Alvarez‑Zavala2 · Mariana del Rocio Ruiz‑Briseño1,2 · José Luis Mosqueda‑Gómez4 · Santiago Avila‑Rios5 · Moises Ramos‑Solano6 · Jaime Federico Andrade‑Villanueva2,3 Received: 9 May 2020 / Accepted: 9 September 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract HIV infects its target cell and integrates into its genome as an essential step in its replication cycle. Proviral DNA is also subjected to the same transcriptional regulation as the host cell genome by its own transcriptional factors, with activating or repressive activity. There is a clear interaction between the presence of transcriptional repressors and a decrease in the rate of HIV replication, promoting gene silencing in infected cells, which serve as viral reservoirs. This represents a major obstacle for HIV eradication. The ZBTB gene family comprises 49 genes that encode transcription factors that have a repressor function in differentiation and development of cells of the lymphopoietic lineage, including the main target cells of HIV, C D4+ T cells. In this cross-sectional study, we evaluated the expression profile of ZBTB genes in C D4+ T cells of HIV-positive individuals with different levels of infection control. We found upregulation of gene expression of ZBTB4 (p < 0.01), ZBTB7B (p < 0.001), and ZBTB38 (p < 0.05) and downregulation of ZBTB16 (p < 0.01) in HIV-positive patients compared to HIV-negative individuals. Interestingly, in a deeper analysis, we observed that elite controllers had the highest levels of expression of the ZBTB38, ZBTB2, HIC1, ZBTB7A, ZBTB7B (ThPOK) and ZBTB4 genes, showing 2.56- to 7.60-fold upregulation compare to the ART-naïve group. These results suggest a possible contribution of these ZBTB transcriptional repressors in HIV-positive patients and a possible new molecular mechanism of viral control.
Handling Editor: Carolina Scagnolari. * Moises Ramos‑Solano [email protected]; [email protected]
Santiago Avila‑Rios [email protected] 1
Molecular Biology in Medicine PhD Program, CUCS, Universidad de Guadalajara, Guadalajara, Mexico
2
HIV and Immunodeficiencies Research Institute, Clinical Medicine Department, CUCS, Universidad de Guadalajara, Guadalajara, Mexico
3
Sarah Ratkovich‑González [email protected]
HIV Unit Department, Antiguo Hospital Civil de Guadalajara “Fray Antonio Alcalde”, OPD Hospitales Civiles, Guadalajara, Jalisco, Mexico
4
Karina Sánchez‑Reyes [email protected]
Hospital Regional de Alta Especialidad del Bajío, León, Guanajuato, México
5
Monserrat Alvarez‑Zavala [email protected]
Center for Research in Infectious Diseases, National Institute of Respiratory Diseases, Tlalpan, Mexico City, Mexico
6
Pathology Laboratory, CUCS, Universidad de Guadalajara, J
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