Transcriptome altered by latent human cytomegalovirus infection on THP-1 cells using RNA-seq

Abstract

Human cytomegalovirus (HCMV) has been recognized as a cause of severe, sometimes life-threatening disease in congenitally infected newborns as well as in immunocompromised individuals. However, the molecular mechanisms of the host-virus interaction remain poorly understood. Here, we profiled the expression of mRNAs and long noncoding RNAs (lncRNAs) in THP-1 cells using the emerging RNA-seq to investigate the transcriptional changes during HCMV latent infection. At 4 days post HCMV infection, a total of 169,008,624 sequence reads and 180,616 transcripts were obtained, respectively. Of these transcripts, 1,354 noncoding genes and 12,952 protein-coding genes were observed in Refseq database. Differential gene expression analysis identified 2,153 differentially expressed genes (DEGs) between HCMV-infected and mock-infected THP-1 cells, including 1,098 up-regulated genes and 1,055 down-regulated genes. These regulated genes were involved in pathways of apoptosis, inflammatory response and cell cycle progression, all of which may be implicated in viral pathogenesis. In addition, 646 lncRNAs (208 known lncRNAs and 438 novel lncRNAs) were upregulated and 424 (140 known and 284 novel) were downregulated in infected THP-1 cells. These findings have provided a dynamic scenario of DE candidate genes and lncRNAs at the virus-host interface and clearly warrant further experimental investigation associated with HCMV infection.

Human cytomegalovirus genomics and transcriptomics through the lens of next-generation sequencing: revision and future challenges

“…As expected, those differentially expressed genes were involved in pathways of apoptosis, inflammatory response and cell cycle progression [ 100 ]. Interestingly, lncRNAs were differentially expressed with an ongoing HCMV latent infection [ 100 ]. A year later, Cheng et al (BioProject PRJNA389726) compared the expression of natural infection (healthy peripheral blood mononuclear cells latently infected with clinically uncharacterized HCMV) and experimental latency system in a transcriptome-wide study using positive strand SureSelect XT target enrichment [ 80 ].…”

“…Although pending for experimental validation, Zhang and colleagues (BioProject PRJNA340198) described the latent HCMV Towne infection cell transcriptome in THP-1 cells [ 100 ], defining more than 2000 host differentially expressed genes, with approximately half of them with an upregulated expression profile. As expected, those differentially expressed genes were involved in pathways of apoptosis, inflammatory response and cell cycle progression [ 100 ]. Interestingly, lncRNAs were differentially expressed with an ongoing HCMV latent infection [ 100 ].…”

Transcriptional Profiling of Midguts Prepared from Trypanosoma/T. congolense-Positive Glossina palpalis palpalis Collected from Two Distinct Cameroonian Foci: Coordinated Signatures of the Midguts’ Remodeling As T. congolense-Supportive Niches

“…In agreement with this, we observed the repression or non-activation of transcription genes that may allow the trypanosome to alter its host’s transcription steps. Furthermore, certain metabolic pathways were downregulated that can prevent the host from synthesizing factors (proteins or metabolites) needed to fight infection ( 71 ). In this context and concerning the “Biological Process,” “Cellular Component,” and “Molecular Function” categories, most of the functional classes were associated with the host transcription/translation machinery (translation, RNA binding, ribonucleoprotein complex, ribosome processing helicase, etc.).…”

Application of Next-Generation Sequencing in the Era of Precision Medicine

“…Applications of NGS in virology diagnostic can be used for analysis of patients with unexplained illness, especially during outbreaks and epidemics [67][68][69][70]. It also includes the identiication of novel pathogens [71][72][73][74], viral community characterization [75][76][77], whole viral genome reconstruction [73,78,79], antiviral drug resistance [80][81][82][83], epidemiology [84][85][86][87] and transcriptomic [88][89][90]. The use of NGS in virology is increasing the knowledge of viral infection dynamics and their correlation with human health and treatment.…”