Background: Women infected with HIV are more likely to have aggressive cervical cancer, and patients with HIV infection are often more severely ill than those without HIV infection. However, the underlying mechanism for the progression of cervical cancer is not yet fully understood and requires further research.

Immune non-responder after highly active antiretroviral therapy (HAART) is the main cause of opportunistic infections and high mortality in AIDS patients, but the mechanism underlying immune reconstitution failure is poorly understood. Here, we performed scRNA-seq, and scATAC-seq analysis of peripheral blood mononuclear cells (PBMCs) derived from immune non-responder (INR) and responder (IR) HIV-1-infected subjects. We found low expression of mucosal-associated invariant T (MAIT) cells in INRs, which exhibited transcriptional profiles associated with impaired mitochondrial function and apoptosis signaling. Single-cell assays for transposase-accessible chromatin (scATAC-seq) and flow cytometry revealed diminished mitochondrial fitness in MAIT cells from INRs, and MAIT had low expression of transcription factor A for mitochondria (TFAM) and peroxisomal proliferator-activated receptor alpha (PPARA). These findings demonstrate that restoring mitochondrial function could modulate the immune dysfunction characteristic of MAIT against bacterial co-infections in INRs subjects.

The functions and mechanisms of long non-coding RNAs (lncRNAs) in latent HIV-1 infection are not yet fully understood and warrant further research. In this study, we identified the newly inhibitory lncRNA AK130181 (also named LOC105747689), which is highly expressed in CD4⁺ T lymphocytes latently infected with HIV, using bioinformatics. We also found that AK130181 is involved in HIV-1 latency by inhibiting long terminal repeat (LTR)-driven HIV-1 gene transcription in a nuclear factor κB (NF-κB)-dependent manner. Furthermore, silencing AK130181 significantly reactivates viral production from HIV-1 latently infected Jurkat T cells and primary CD4⁺ T cells. Interestingly, we found that inhibition of AK130181 in resting CD4⁺ T cells from HIV-1-infected individuals treated with highly active antiretroviral therapy significantly increased viral reactivation upon T cell activation in vivo. We provide new insights and a better understanding of lncRNAs that play a role in HIV-1 latency, and suggest that silencing AK130181 expression to activate HIV-1 latently infected cells may be a potential therapeutic target for HIV-infected individuals.

Immune non-responder (INR) after highly active antiretroviral therapy (HAART) is the main cause of opportunistic infection and high mortality in AIDS patients, but the mechanism underlying immune reconstitution failure is poorly understood. Here we performed scRNA-seq and scATAC-seq analysis of peripheral blood mononuclear cells (PBMCs) derived from Immune nonresponder (INR) and responder (IR) HIV-1-infected subjects. We then describe the mitochondrial function of MAIT by flow cytometry in INRs and IRs. We founded there were diminished frequencies and numbers of MAIT cells in INRs, and MAIT cells from INRs displayed transcriptional profiles associated with the impairment of mitochondrial function and apoptosis signaling. ScATAC-seq and flow cytometry revealed diminished mitochondrial fitness in MAIT cells from INRs, and MAIT had low expression of transcription factor A for mitochondria (TFAM) and PPARA. These findings demonstrate the restoring mitochondrial function could modulate the immune dysfunction characteristic of MAIT, which against bacterial co-infections in INRs subjects.

This study aimed to investigate whether mutations in the rv2005c, PPE59, and recC genes are associated with fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis (Mtb), particularly in strains lacking mutations in the known resistance genes gyrA and gyrB. A total of 275 clinical isolates, consisting of 217 pre-extensively drug-resistant strains and 58 fluoroquinolone-sensitive strains, were included in this study. Gene sequencing was performed on all isolates, and functional assessments through both overexpression and knockout experiments of the gene were conducted to evaluate its effect on fluoroquinolone susceptibility. Results: Among 275 isolates, no mutations were detected in PPE59 or recC. In the 217 pre-XDR isolates, gyrA mutations were found in 214 (98.6%), predominantly at codons 94, 90, and 91. Only two isolates harbored synonymous mutations in rv2005c (P235P), both with concurrent gyrA D94G mutations. Overexpression or knockout of rv2005c in Mtb did not alter FQ susceptibility. Notably, two FQ-resistant isolates lacked mutations in any of the five genes sequenced, suggesting the presence of unknown resistance mechanisms. Our results showed that mutations of the rv2005c, PPE59 and recC genes may not contribute to FQ resistance in clinical isolates of Mtb in Chongqing, China. Furthermore, our study results also showcased the complexity of mechanisms of FQ resistance in clinical Mtb isolates.