MicroRNA-150 is a potential biomarker of HIV/AIDS disease progression and therapy.
BACKGROUND
The surrogate markers of HIV/AIDS progression include CD4 T cell count and plasma viral load. But, their reliability has been questioned in patients on anti-retroviral therapy (ART). Five microRNAs (miRNAs) - miR-16, miR-146b-5p, miR-150, miR-191 and miR-223 in peripheral blood mononuclear cells (PBMCs) were earlier found to assign HIV/AIDS patients into groups with varying CD4 T cell counts and viral loads. In this pilot study, we profiled the expression of these five miRNAs in PBMCs, and two of these miRNAs (miR-146b-5p and miR-150) in the plasma of HIV/AIDS patients, including those on ART and those who developed ART resistance, to evaluate if these are biomarkers of disease progression and therapy.


RESULTS
We quantified miRNA levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RNA isolated from PBMCs and plasma of healthy persons or HIV-infected patients who were (1) asymptomatic; (2) symptomatic and ART naïve; (3) on ART; and (4) failing ART. Our results show miR-150 (p<0.01) and to a lesser extent miR-146b-5p (p<0.05) levels in PBMCs to reliably distinguish between ART-naïve AIDS patients, those on ART, and those developing drug resistance and failing ART. The plasma levels of these two miRNAs also varied significantly between patients in these groups and between patients and healthy controls (p values <0.05).


CONCLUSIONS
We report for the first time that PBMC and plasma levels of miR-150 and miR-146b-5p are predictive of HIV/AIDS disease progression and therapy.
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Saif Ullah
SU
Munshi
ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Harekrushna
H
Panda
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Prasida
P
Holla
ART Department, National AIDS Control Organization and Dr. Ram Manohar Lohia Hospital, New Delhi, India.
Bharat Bhushan
BB
Rewari
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Shahid
S
Jameel
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000821:virology; D000328:Adult; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D018450:Disease Progression; D024882:Drug Resistance, Viral; D005260:Female; D005786:Gene Expression Regulation; D006678:HIV / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D019829:Nevirapine / Q000627:therapeutic use; D018119:Stavudine / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D015215:Zidovudine / Q000627:therapeutic use
D000480:Alkynes; D048588:Benzoxazines; D015415:Biomarkers; D003521:Cyclopropanes; D019259:Lamivudine; D035683:MicroRNAs; D019829:Nevirapine; D018119:Stavudine; D015215:Zidovudine; C542542:MIRN146 microRNA, human; C533097:MIR150, human; C098320:efavirenz