Differential Expression of lncRNAs in HIV Patients with TB and HIV-TB with Anti-Retroviral Treatment.

Tuberculosis (TB) is the leading cause of death among people with HIV-1 infection. To improve the diagnosis and treatment of HIV-TB patients, it is important to understand the mechanisms underlying these conditions. Here, we used an integrated genomics approach to analyze and determine the lncRNAs that are dysregulated in HIV-TB patients and HIV-TB patients undergoing anti-retroviral therapy (ART) using a dataset available in the public domain. The analyses focused on the portion of the genome transcribed into non-coding transcripts, which historically have been poorly studied and received less focus. This revealed that Mtb infection in HIV prominently up-regulates the expression of long non-coding RNA (lncRNA) genes DAAM2-AS1 , COL4A2-AS1 , LINC00599 , AC008592.1 , and CLRN1-AS1 and down-regulates the expression of lncRNAs AC111000.4 , AC100803.3 , AC016168.2 , AC245100.7 , and LINC02073 . It also revealed that ART down-regulates the expression of some lncRNA genes ( COL4A2-AS1 , AC079210.1 , MFA-AS1 , and LINC01993 ) that are highly up-regulated in HIV-TB patients. Furthermore, the interrogation of the genomic regions that are associated with regulated lncRNAs showed enrichment for biological processes linked to immune pathways in TB-infected conditions. However, intriguingly, TB patients treated with ART showed completely opposite and non-overlapping pathways. Our findings suggest that lncRNAs could be used to identify critical diagnostic, prognostic, and treatment targets for HIV-TB patients.