Characterization of CD8+ T-cell response in acute and resolved hepatitis A virus infection

Schulte, I.; Hitziger, Tobias; Giugliano, Silvia; Timm, Joerg; Gold, HL; Heinemann, Falko M.; Khudyakov, Yury; Straßer, Michael; König, Christoph; Castermans, Emilie; Mok, Juk Yee; Esch, Wim J. E. van; Bertoletti, Antonio; Schumacher, Ton N.; Roggendorf, Michael

doi:10.1016/j.jhep.2010.07.010

Cited by 33 publications

(26 citation statements)

References 20 publications

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“…However, a series of recent studies have provided fresh insight into cellular immune responses using newer methods for more precise measurement of T cell frequency and function. Epitopes presented by defined class I epitopes were mapped in human subjects infected during a recent hepatitis A outbreak [31]. Whereas CD8+ T cells targeting these epitopes were successfully expanded from blood of patients with acute HAV infection, most circulating CD8+ T cells were present at frequencies too low for direct visualization with class I tetramers.…”

Section: Adaptive Immunity and Control Of Hav Infectionmentioning

confidence: 99%

Reassessing immune control of hepatitis A virus

Walker

Feng

Lemon

2015

Current Opinion in Virology

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There is renewed interest in hepatitis A virus (HAV) pathogenesis and immunity after 2–3 decades of limited progress. From a public health perspective, the average age at infection has increased in developing countries, resulting in more severe hepatitis that is poorly understood mechanistically. More fundamentally, there is interest in comparing immunity to HAV and hepatitis C virus (HCV): small, positive-strand RNA viruses with very different infection outcomes. Here, we review evidence that circulating HAV virions are cloaked in membranes, with consequences for induction of innate immunity and antibody-mediated neutralization. We also consider the contribution of CD4+ helper versus CD8+ cytotoxic T cells to antiviral immunity and liver injury, and present a model of non-cytotoxic immune control of HAV infection.

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Section: Adaptive Immunity and Control Of Hav Infectionmentioning

confidence: 99%

Reassessing immune control of hepatitis A virus

Walker

Feng

Lemon

2015

Current Opinion in Virology

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“…Investigating virus‐specific T‐cell responses against non‐structural proteins is of interest since this part of the virus genome can also be immunogenic and studies for vaccine development against human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have shown the importance of a broad and multifunctional anti‐viral T‐cell response for virus clearance . For most viruses, T‐cell responses against the entire genome have been described . HCV‐specific T‐cell responses target proteins encoded by the entire HCV genome with no major preferences to specific HCV proteins, whereas in HIV infection T‐cell responses are more frequently detected against p24‐Gag and Nef …”

Section: Introductionmentioning

confidence: 99%

Hepatitis E virus ORF 1 induces proliferative and functional T‐cell responses in patients with ongoing and resolved hepatitis E

Al-Ayoubi

Behrendt

Bremer

et al. 2017

Liver International

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“…T cells also appear to be important for HAV clearance [5], [6]. In both cases, the vigor and breadth of the virus-specific T response is likely to be profoundly influenced by early interferon (IFN) and other cytokine responses evoked by innate antiviral response pathways.…”

Section: Introductionmentioning

confidence: 99%

Disruption of TLR3 Signaling Due to Cleavage of TRIF by the Hepatitis A Virus Protease-Polymerase Processing Intermediate, 3CD

Feng²,

Yamane³

et al. 2011

PLoS Pathog

126

110

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Toll-like receptor 3 (TLR3) and cytosolic RIG-I-like helicases (RIG-I and MDA5) sense viral RNAs and activate innate immune signaling pathways that induce expression of interferon (IFN) through specific adaptor proteins, TIR domain-containing adaptor inducing interferon-β (TRIF), and mitochondrial antiviral signaling protein (MAVS), respectively. Previously, we demonstrated that hepatitis A virus (HAV), a unique hepatotropic human picornavirus, disrupts RIG-I/MDA5 signaling by targeting MAVS for cleavage by 3ABC, a precursor of the sole HAV protease, 3Cpro, that is derived by auto-processing of the P3 (3ABCD) segment of the viral polyprotein. Here, we show that HAV also disrupts TLR3 signaling, inhibiting poly(I:C)-stimulated dimerization of IFN regulatory factor 3 (IRF-3), IRF-3 translocation to the nucleus, and IFN-β promoter activation, by targeting TRIF for degradation by a distinct 3ABCD processing intermediate, the 3CD protease-polymerase precursor. TRIF is proteolytically cleaved by 3CD, but not by the mature 3Cpro protease or the 3ABC precursor that degrades MAVS. 3CD-mediated degradation of TRIF depends on both the cysteine protease activity of 3Cpro and downstream 3Dpol sequence, but not 3Dpol polymerase activity. Cleavage occurs at two non-canonical 3Cpro recognition sequences in TRIF, and involves a hierarchical process in which primary cleavage at Gln-554 is a prerequisite for scission at Gln-190. The results of mutational studies indicate that 3Dpol sequence modulates the substrate specificity of the upstream 3Cpro protease when fused to it in cis in 3CD, allowing 3CD to target cleavage sites not normally recognized by 3Cpro. HAV thus disrupts both RIG-I/MDA5 and TLR3 signaling pathways through cleavage of essential adaptor proteins by two distinct protease precursors derived from the common 3ABCD polyprotein processing intermediate.

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Characterization of CD8+ T-cell response in acute and resolved hepatitis A virus infection

Cited by 33 publications

References 20 publications

Reassessing immune control of hepatitis A virus

Reassessing immune control of hepatitis A virus

Hepatitis E virus ORF 1 induces proliferative and functional T‐cell responses in patients with ongoing and resolved hepatitis E

Disruption of TLR3 Signaling Due to Cleavage of TRIF by the Hepatitis A Virus Protease-Polymerase Processing Intermediate, 3CD

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