HIV-SEQ REVEALS GLOBAL HOST GENE EXPRESSION DIFFERENCES BETWEEN HIV-TRANSCRIBING CELLS FROM VIREMIC AND SUPPRESSED PEOPLE WITH HIV DOI Creative Commons
Julie Frouard, Sushama Telwatte, Xiaoyu Luo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract “Active” reservoir cells transcribing HIV can perpetuate chronic inflammation in virally suppressed people with (PWH) and likely contribute to viral rebound after antiretroviral therapy (ART) interruption, so they represent an important target for new therapies. These cells, however, are difficult study using single-cell RNA-seq (scRNA-seq) due their low frequency levels of transcripts, which usually not polyadenylated. Here, we developed “HIV-seq” enable more efficient capture transcripts – including non-polyadenylated ones scRNA-seq analysis from PWH. By spiking a set custom-designed sequences targeting conserved regions the genome during scRNA-seq, increased our ability find RNA+ PWH by up 44%. Implementing HIV-seq conjunction surface phenotyping CITE-seq on paired blood specimens before vs. ART suppression, found that were enriched among T effector memory (Tem) both viremia but exhibited cytotoxic signature only. contrast, ART-suppressed timepoints distinct anti-inflammatory involving elevated TGF-β diminished IFN signaling. Overall, these findings demonstrate active exhibit transcriptional features viremia, underscore as useful tool better understand mechanisms HIV-transcribing persist ART.

Language: Английский

Post-Transcriptional HIV-1 Latency: A Promising Target for Therapy? DOI Creative Commons
Mie Kobayashi‐Ishihara, Yasuko Tsunetsugu‐Yokota

Viruses, Journal Year: 2024, Volume and Issue: 16(5), P. 666 - 666

Published: April 24, 2024

Human Immunodeficiency Virus type 1 (HIV-1) latency represents a significant hurdle in finding cure for HIV-1 infections, despite tireless research efforts. This challenge is partly attributed to the intricate nature of latency, wherein various host and viral factors participate multiple physiological processes. While substantial progress has been made discovering therapeutic targets transcription, post-transcriptional regulation infections have received less attention. However, cumulative evidence now suggests pivotal contribution both vitro models infected individuals. In this review, we explore recent insights on discuss potential its targets, illustrating some that restrict at level.

Language: Английский

Citations

3
Integrated Genetic and Cellular Analysis Reveals NLRP1 Activation in CD4+ T Lymphocytes During Chronic HIV Infection DOI
Vinícius Nunes Cordeiro Leal, Mariela Estefany Gislene Vera Roa,

Julia Silva Cantoni

et al.

Immunological Investigations, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 20

Published: Nov. 4, 2024

Background Most of the investigations related to inflammasome activation during HIV infection have focused on receptor NLRP3 and innate immune cells such as monocytes/macrophages. However, past years, has also been explored in lymphocytes, novel sensors, other than NLRP3, shown play a role biology these cells. Here, we hypothesized that NLRP1 may be involved CD4+ T cell dysregulation people living with (PLWH), therefore contributing chronic inflammation pathogenesis non-HIV-associated diseases.

Language: Английский

Citations

0
HIV-SEQ REVEALS GLOBAL HOST GENE EXPRESSION DIFFERENCES BETWEEN HIV-TRANSCRIBING CELLS FROM VIREMIC AND SUPPRESSED PEOPLE WITH HIV DOI Creative Commons
Julie Frouard, Sushama Telwatte, Xiaoyu Luo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

Abstract “Active” reservoir cells transcribing HIV can perpetuate chronic inflammation in virally suppressed people with (PWH) and likely contribute to viral rebound after antiretroviral therapy (ART) interruption, so they represent an important target for new therapies. These cells, however, are difficult study using single-cell RNA-seq (scRNA-seq) due their low frequency levels of transcripts, which usually not polyadenylated. Here, we developed “HIV-seq” enable more efficient capture transcripts – including non-polyadenylated ones scRNA-seq analysis from PWH. By spiking a set custom-designed sequences targeting conserved regions the genome during scRNA-seq, increased our ability find RNA+ PWH by up 44%. Implementing HIV-seq conjunction surface phenotyping CITE-seq on paired blood specimens before vs. ART suppression, found that were enriched among T effector memory (Tem) both viremia but exhibited cytotoxic signature only. contrast, ART-suppressed timepoints distinct anti-inflammatory involving elevated TGF-β diminished IFN signaling. Overall, these findings demonstrate active exhibit transcriptional features viremia, underscore as useful tool better understand mechanisms HIV-transcribing persist ART.

Language: Английский

Citations

0