RGD Reference Report - Direct antiviral agents upregulate natural killer cell potential activity in chronic hepatitis C patients. - Rat Genome Database

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Direct antiviral agents upregulate natural killer cell potential activity in chronic hepatitis C patients.

Authors: Jiang, Han-Ji  Wang, Xiao-Xiao  Luo, Bi-Fen  Cong, Xu  Jin, Qian  Qin, Hong  Zhang, Hai-Ying  Kong, Xiang-Sha  Wei, Lai  Feng, Bo 
Citation: Jiang HJ, etal., Clin Exp Med. 2019 Aug;19(3):299-308. doi: 10.1007/s10238-019-00564-9. Epub 2019 Jun 20.
RGD ID: 40400920
Pubmed: PMID:31218578   (View Abstract at PubMed)
DOI: DOI:10.1007/s10238-019-00564-9   (Journal Full-text)

Direct antiviral agents (DAAs) can eliminate hepatitis C virus rapidly and make chronic hepatitis C (CHC) curable. The changes in the innate immune system during treatment with DAAs are still in dispute. To investigate how the functions of natural killer (NK) cells change during and after treatment with DAAs in each NK cell subset. Thirteen CHC patients were treated with sofosbuvir/ledipasvir, and the expression levels of NKp46 and NKG2A were tested via flow cytometry at baseline, at 2, 4, 8 and 12 weeks during the therapy and 12 and 24 weeks after the end of treatment; expression levels were compared between CHC patients and 13 healthy controls. A redirected killing assay was used to detect the cytotoxicity of NK cells. After coculturing NK cells with JFH-Huh7 cells for 72 h, HCV RNA was tested to analyze the inhibition ability of NK cells. All patients achieved sustained virologic response. The expression of the activating receptor NKp46 was decreased first at week 8 during therapy with DAAs and then increased and normalized to levels in healthy controls after treatment with DAAs. The expression of the inhibitory receptor NKG2A was decreased during and after treatment with DAAs. Each NK cell subset has a similar changing trend during and after treatment with DAAs, although some differences can be found earlier and later. The ratio of NKp46 and NKG2A was upregulated after treatment with DAAs. CD56bright NK cells have less amplitude in the frequency ratio changes after treatment with DAAs. The coculture results showed that both the specific lysis and the inhibition of HCV replication were significantly upregulated after treatment with DAAs. DAA treatments can affect patients' NK cell function. After DAA treatments, the expression of functional markers is downregulated, but the potential activity of NK cells is upregulated. The function of NK cells is normalized to levels in healthy controls. CD56bright NK cells play an important role in this process.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Chronic Hepatitis C treatmentIEP 40400920; 40400920 RGD 
Chronic Hepatitis C treatmentISOKLRC1 (Homo sapiens)40400920; 40400920 RGD 
Chronic Hepatitis C treatmentISONCR1 (Homo sapiens)40400920; 40400920 RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ledipasvir decreases expression EXP 40400920ledipasvir co-treated with sofosbuvir decreases expression of NCR1 protein in natural killer cellsRGD 
ledipasvir decreases expression ISOKLRC1 (Homo sapiens)40400920; 40400920ledipasvir co-treated with sofosbuvir decreases expression of NCR1 protein in natural killer cellsRGD 
ledipasvir affects expression EXP 40400920ledipasvir co-treated sofosbuvir with affects expression of NCR1 protein in natural killer cellsRGD 
ledipasvir affects expression ISONCR1 (Homo sapiens)40400920; 40400920ledipasvir co-treated sofosbuvir with affects expression of NCR1 protein in natural killer cellsRGD 
sofosbuvir decreases expressionEXP 40400920sofosbuvir co-treated with ledipasvir decreases expression of NCR1 protein in natural killer cellsRGD 
sofosbuvir decreases expression ISOKLRC1 (Homo sapiens)40400920; 40400920sofosbuvir co-treated with ledipasvir decreased expression of NCR1 protein in natural killer cellsRGD 
sofosbuvir affects expression EXP 40400920sofosbuvir co-treated with ledipasvir affects expression of NCR1 protein in natural killer cellsRGD 
sofosbuvir affects expression ISONCR1 (Homo sapiens)40400920; 40400920sofosbuvir co-treated with ledipasvir affects expression of NCR1 protein in natural killer cellsRGD 

Objects Annotated

Genes (Rattus norvegicus)
Klrc1  (killer cell lectin like receptor C1)
Ncr1  (natural cytotoxicity triggering receptor 1)

Genes (Mus musculus)
Klrc1  (killer cell lectin-like receptor subfamily C, member 1)
Ncr1  (natural cytotoxicity triggering receptor 1)

Genes (Homo sapiens)
KLRC1  (killer cell lectin like receptor C1)
NCR1  (natural cytotoxicity triggering receptor 1)


Additional Information