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Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV

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ABSTRACT

Background: Infection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20–46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA) between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance.

Methods: Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV.

Results: We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR) <0.05) before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF) are associated with innate immune response functions.

Conclusions: These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.

No MeSH data available.


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Intersectional analysis of the differentially expressed genes before and after HCV infection in clearance group and Chronic group. The diagram was generated with the statistical differentially expressed genes between clearance group and chronic group before and after HCV infection
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Fig4: Intersectional analysis of the differentially expressed genes before and after HCV infection in clearance group and Chronic group. The diagram was generated with the statistical differentially expressed genes between clearance group and chronic group before and after HCV infection

Mentions: Intersection analyses between DEGs identified in the clearance group before HCV infection (DEG-B, Fig. 1) and after HCV infection (DEG-A, Fig. 1) indicate that 12 DEGs were uniquely expressed in clearance group before HCV infection and 36 DEGs were uniquely expressed after HCV infection (Fig. 4). There were 21 DEGs that were common between the two groups. IPA analyses of these unique 12 genes expressed before HCV infection indicate that a number of these genes and their upstream regulators are associated with innate immune response in the clearance group (Fig. 5a and b). Among them 14% are involved in immune cell trafficking, 14% are involved in humoral immune response and 14% are involved in cell mediated immune response suggesting that most of the unique DEGs in the clearance group before infection may play a role in defending against the virus (Fig. 5a). For instance, cytokine (such as IL-1, IL-4, IL-6, IL-8, IL-9, IL-10, TNFR1, interferon) signaling, Toll like receptor (TLR) signaling, MAPK signaling, NF-κB signaling, and communication between innate and adaptive immune cells may be involved (Fig. 5b). Similar analyses with 36 DEGs after HCV infection found that these genes are involved in glucocorticoid receptor signaling, myc mediated apoptosis signaling, axonal guidance signaling, IGF1 signaling, MAPK signaling, p53 signaling, PI3K/AKT signaling, and acute phase response signaling.Fig. 4


Identification of the transcripts associated with spontaneous HCV clearance in individuals co-infected with HIV and HCV
Intersectional analysis of the differentially expressed genes before and after HCV infection in clearance group and Chronic group. The diagram was generated with the statistical differentially expressed genes between clearance group and chronic group before and after HCV infection
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5120459&req=5

Fig4: Intersectional analysis of the differentially expressed genes before and after HCV infection in clearance group and Chronic group. The diagram was generated with the statistical differentially expressed genes between clearance group and chronic group before and after HCV infection
Mentions: Intersection analyses between DEGs identified in the clearance group before HCV infection (DEG-B, Fig. 1) and after HCV infection (DEG-A, Fig. 1) indicate that 12 DEGs were uniquely expressed in clearance group before HCV infection and 36 DEGs were uniquely expressed after HCV infection (Fig. 4). There were 21 DEGs that were common between the two groups. IPA analyses of these unique 12 genes expressed before HCV infection indicate that a number of these genes and their upstream regulators are associated with innate immune response in the clearance group (Fig. 5a and b). Among them 14% are involved in immune cell trafficking, 14% are involved in humoral immune response and 14% are involved in cell mediated immune response suggesting that most of the unique DEGs in the clearance group before infection may play a role in defending against the virus (Fig. 5a). For instance, cytokine (such as IL-1, IL-4, IL-6, IL-8, IL-9, IL-10, TNFR1, interferon) signaling, Toll like receptor (TLR) signaling, MAPK signaling, NF-κB signaling, and communication between innate and adaptive immune cells may be involved (Fig. 5b). Similar analyses with 36 DEGs after HCV infection found that these genes are involved in glucocorticoid receptor signaling, myc mediated apoptosis signaling, axonal guidance signaling, IGF1 signaling, MAPK signaling, p53 signaling, PI3K/AKT signaling, and acute phase response signaling.Fig. 4

View Article: PubMed Central - PubMed

ABSTRACT

Background: Infection with human immunodeficiency virus (HIV) influences the outcome and natural disease progression of hepatitis C virus (HCV) infection. While the majority of HCV mono-infected and HCV/HIV co-infected subjects develop chronic HCV infection, 20–46% of mono- and co-infected subjects spontaneously clear HCV infection. The mechanism underlying viral clearance is not clearly understood. Analysis of differential cellular gene expression (mRNA) between HIV-infected patients with persistent HCV infection or spontaneous clearance could provide a unique opportunity to decipher the mechanism of HCV clearance.

Methods: Plasma RNA from HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV was sequenced using Ion Torrent technology. The sequencing results were analyzed to identify transcripts that are associated with HCV clearance by measuring differential gene expression in HIV/HCV co-infected subjects who cleared HCV and those who remained chronically infected with HCV.

Results: We have identified plasma mRNA, the levels of which are significantly elevated (at least 5 fold, False Discovery Rate (FDR) <0.05) before HCV infection in subjects who cleared HCV compared to those who remained chronically infected. Upon further analysis of these differentially expressed genes, before and after HCV infection, we found that before HCV infection 12 genes were uniquely upregulated in the clearance group compared to the chronically infected group. Importantly, a number of these 12 genes and their upstream regulators (such as CCL3, IL17D, LBP, SOCS3, NFKBIL1, IRF) are associated with innate immune response functions.

Conclusions: These results suggest that subjects who spontaneously clear HCV may express these unique genes associated with innate immune functions.

No MeSH data available.


Related in: MedlinePlus