Host-Microbe interactions and transcriptomics during SIV infection with or without antiretroviral therapy

Gut dysbiosis and microbial translocation contribute to chronic immune activation and inflammation in HIV infection. Even under antiretroviral therapy (ART), the gut microbiota is not restored to the level of healthy compositions.

Our lab developed a software to analyze the transcriptome for both host and microbiome and study the association of host and pathogen interaction under SIV infection on or off ART.

For more information about the MTD software:

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  • Siddiqui, Summer, Duran Bao, Lara Doyle-Meyers, Jason Dufour, Yuntao Wu, Yao-Zhong Liu, and Binhua Ling. (2020) 2020. “Alterations of the Gut Bacterial Microbiota in Rhesus Macaques With SIV Infection and on Short- or Long-Term Antiretroviral Therapy.”. Scientific Reports 10 (1): 19056. https://doi.org/10.1038/s41598-020-76145-8.

    Gut dysbiosis and microbial translocation are associated with chronic systemic immune activation and inflammation in HIV-1 infection. However, the extent of restoration of gut microbiota in HIV-1 patients with short or long-term antiretroviral therapy (ART) is unclear. To understand the impact of ART on the gut microbiota, we used the rhesus macaque model of SIV infection to characterize and compare the gut microbial community upon SIV infection and during ART. We observed altered taxonomic compositions of gut microbiota communities upon SIV infection and at different time points of ART. SIV-infected animals showed decreased diversity of gut microbiome composition, while the ART group appeared to recover towards the diversity level of the healthy control. Animals undergoing ART for various lengths of time were observed to have differential gut bacterial abundance across different time points. In addition, increased blood lipopolysaccharide (LPS) levels during SIV infection were reduced to near normal upon ART, indicating that microbial translocation and immune activation can be improved during therapy. In conclusion, while short ART may be related to transient increase of certain pathogenic bacterial microbiome, ART may promote microbiome diversity compromised by SIV infection, improve the gut microbiota towards the healthy compositions and alleviate immune activation.

  • Wu, Fei, Yao-Zhong Liu, and Binhua Ling. (2022) 2022. “MTD: a Unique Pipeline for Host and Meta-Transcriptome Joint and Integrative Analyses of RNA-Seq Data.”. Briefings in Bioinformatics 23 (3). https://doi.org/10.1093/bib/bbac111.

    Ribonucleic acid (RNA)-seq data contain not only host transcriptomes but also nonhost information that comprises transcripts from active microbiota in the host cells. Therefore, joint and integrative analyses of both host and meta-transcriptome can reveal gene expression of the microbial community in a given sample as well as the correlative and interactive dynamics of the host response to the microbiome. However, there are no convenient tools that can systemically analyze host-microbiota interactions through simultaneously quantifying the host and meta-transcriptome in the same sample at the tissue and the single-cell level. This poses a challenge for interested researchers with limited expertise in bioinformatics. Here, we developed a software pipeline that can comprehensively and synergistically analyze and correlate the host and meta-transcriptome in a single sample using bulk and single-cell RNA-seq data. This pipeline, named meta-transcriptome detector (MTD), can extensively identify and quantify microbiome, including viruses, bacteria, protozoa, fungi, plasmids and vectors, in the host cells and correlate the microbiome with the host transcriptome. MTD is easy to install and run, involving only a few lines of simple commands. It offers researchers with unique genomics insights into host responses to microorganisms.