Hepatitis C Virus: Strategies to Evade Antiviral Responses

Gokhale, Nandan S.; Vazquez, Christine; Horner, Stacy M.

doi:10.2217/fvl.14.89

Cited by 35 publications

(34 citation statements)

References 142 publications

(196 reference statements)

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“…The type I IFN system presents important innate immunity to effectively block virus replication (Jones et al, 2005;Morrison et al, 2013). HCV infection has been reported to inhibit antiviral IFN responses that facilitate virus replication by promoting the HCV NS3/ 4A protease-mediated cleavage of mitochondrial antiviralsignaling protein (MAVS)/TIR-domain-containing adapterinducing interferon-b (TRIF) (Gokhale et al, 2014). In the present study, we found that a natural product celastrol could effectively inhibit HCV NS3/4A protease activity and enhance IFN-mediated antiviral gene expression through HO-1 induction (Figs.…”

Section: Discussionmentioning

confidence: 99%

Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells

et al. 2017

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“…Though the path to the active site is not very narrow, measuring from 17.2 Å to 20.5 Å between Trp126, Gln181, and Lys314, a relatively small peptide or other viral product capable of binding at or near these side groups could easily interfere with oligo synthesis. Four of these sites (and indeed most of the positively selected sites throughout the protein) are found in superficial loops which exposes them as potential targets for viral proteases in a similar fashion to hepatitis C virus N3/4A, which cleaves the antiviral MAVS protein (Gokhale, et al 2014). …”

Section: Discussionmentioning

confidence: 99%

Functional evolution of the OAS1 viral sensor: Insights from old world primates

Fish

Boissinot

2016

Infection, Genetics and Evolution

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Infections with viral pathogens impose considerable selective pressure on host defensive genes. Those genes at the forefront, responsible for identifying and binding exogenous molecular viral components, will carry the hallmarks of this struggle. Oligoadenylate synthetase (OAS) enzymes play a major role in the innate defense against a large number of viruses by acting as sensors of viral infections. Following their up-regulation by the interferon pathway, OASs bind viral dsRNA and then signal ribonuclease L (RNase L) to degrade RNA, shutting down viral and host protein synthesis. We have investigated the evolution of OAS1 in twenty-two Old World monkey species. We identified a total of 35 codons with the earmarks of positive selection and we performed a comprehensive analysis of their functional significance using in silico modeling of the OAS1 protein. Subdividing OAS1 into functional domains revealed intense purifying selection in the active domain but significant positive directional selection in the RNA-binding domain (RBD), the region where OAS1 binds viral dsRNA. The modeling analysis revealed a concentration of rapidly evolving residues in one region of the RBD suggestive of the sub-functionalization of different regions of the RBD. This analysis also identified several positively selected residues circumscribing the entry to the active site suggesting adaptive evasion of viral antagonism and/or selection for production of oligoadenylate of different length.

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“…Of the infectious agents identified with cancer, hepatitis C virus evades antiviral systems by modulating the function of innate immune proteins, including the signalling adaptor protein MAVS (mitochondrial antiviral-signalling protein) (Gokhale et al 2014). Research shows how PAMPS trigger signalling, and that HCV, EBV, KSHV and Papillomaviridae have mechanisms for evading the immune responses (Navratil et al 2010).…”

Section: Cancerous and Non-cancerous Infectious Agentsmentioning

confidence: 99%

The human immune system’s response to carcinogenic and other infectious agents transmitted by mosquito vectors

Johansson

Ward

2016

Parasitol Res

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It has been hypothesised that mosquitoes [Diptera: Culicidae] may play more of a role in certain cancers than is currently appreciated. Research links 33 infectious agents to cancer, 27 of which have a presence in mosquitoes, and that, in addition, mosquito saliva downregulates the immune system. The objective of this paper is to review the literature on the immune system and cancer-causing infectious agents, particularly those present in mosquitoes, with a view to establishing whether such infectious agents can, in the long run, defeat the immune system or be defeated by it. Many of the viruses, bacteria and parasites recognised by the International Agency for Research on Cancer (IARC) as carcinogenic and suspected by others as being involved in cancer have evolved numerous complex ways of avoiding, suppressing or altering the immune system's responses. These features, coupled with the multiplicity and variety of serious infectious agents carried by some species of mosquitoes and the adverse effects on the immune system of mosquito saliva, suggest that postmosquito bite the immune system is likely to be overwhelmed. In such a situation, immunisation strategies offer little chance of cancer prevention, unless a single or limited number of critical infectious agents can be isolated from the 'mosquito' cocktail. If that proves to be impossible cancer prevention will, therefore, if the hypothesis proves to be correct, rest on the twin strategies of environmentally controlling the mosquito population and humans avoiding being bitten. The latter strategy will involve determining the factors that demark those being bitten from those that are not.

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Hepatitis C Virus: Strategies to Evade Antiviral Responses

Cited by 35 publications

References 142 publications

Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells

Celastrol inhibits hepatitis C virus replication by upregulating heme oxygenase-1 via the JNK MAPK/Nrf2 pathway in human hepatoma cells

Functional evolution of the OAS1 viral sensor: Insights from old world primates

The human immune system’s response to carcinogenic and other infectious agents transmitted by mosquito vectors

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