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Expression levels of the innate response gene RIG-I and its regulators RNF125 and TRIM25 in HIV-1-infected adult and pediatric individuals

Britto, Alan M.A.a; Amoedo, Nívea D.b; Pezzuto, Paulaa; Afonso, Adriana O.a; Martínez, Ana M.B.c; Silveira, Jussarac; Sion, Fernando S.d; Machado, Elizabeth S.e; Soares, Marcelo A.a,f; Giannini, Ana L.M.a

doi: 10.1097/QAD.0b013e328361cfbf
Basic Science: Concise Communication

Objective: TLRs (Toll-like receptors) and RLRs (RIG-I-like receptors) mediate innate immune responses by detecting microorganism invasion. RIG-I activation results in the production of interferon (IFN) type 1 and IFN responsive genes (ISGs). As the ubiquitin ligases RNF125 and TRIM25 are involved in regulating RIG-I function, our aim was to assess whether the levels of these three genes vary between healthy and HIV-infected individuals and whether these levels are related to disease progression.

Design: Gene expression analyses for RIG-I, RNF125, and TRIM25 were performed for HIV-infected adults and the children's peripheral blood mononuclear cells (PBMCs).

Methods: Reverse transcription-quantitative PCRs (RT-qPCRs) were performed in order to quantify the expression levels of RIG-I, RNF125 and TRIM25 from PBMCs purified from control or HIV-infected individuals.

Results: Controls express higher levels of the three genes when compared to HIV-infected patients. These expressions are clearly distinct between healthy and progressors, and are reproduced in adults and children. In controls, RNF125 is the highest expressed gene, whereas in progressors, RIG-I is either the highest expressed gene or is expressed similarly to RNF125 and TRIM25.

Conclusion: A pattern of expression of RIG-I, RNF125, and TRIM25 genes in HIV patients is evident. The high expression of RNF125 in healthy individuals reflects the importance of keeping RIG-I function off, inhibiting unnecessary IFN production. Consistent with this assumption, RNF125 levels are lower in HIV patients and importantly, the RNF125/RIG-I ratio is lower in patients who progress to AIDS. Our results might help to predict disease progression and unveil the role of poorly characterized host genes during HIV infection.

aDepartamento de Genética, Instituto de Biologia

bInstituto de Bioquímica Médica, UFRJ, Rio de Janeiro

cFaculdade de Medicina, UFRG, Rio Grande

dHospital Universitário Gaffrée e Guinle, UNIRIO

eInstituto de Puericultura e Pediatria Martagão Gesteira, UFRJ

fPrograma de Genética, INCA, Rio de Janeiro, Brazil.

Correspondence to Ana Lúcia M. Giannini, CCS-Departamento de Genética, Instituto de Biologia, UFRJ, Rua Rodolpho P. Rocco, s/n, Bl. A, room A2-066, Ilha do Fundão, CEP 21941-617, Rio de Janeiro, RJ, Brazil. E-mail: ana.giannini@biologia.ufrj.br

Received 14 September, 2012

Revised 26 March, 2013

Accepted 3 April, 2013

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© 2013 Lippincott Williams & Wilkins, Inc.