Marked Endotheliotropism of Highly Pathogenic Avian Influenza Virus H5N1 following Intestinal Inoculation in Cats

Reperant, Leslie A.; Bildt, Marco W. G. van de; Amerongen, Geert van; Leijten, Lonneke; Watson, Simon J.; Palser, Anne L.; Kellam, Paul; Eissens, Anko C.; Frijlink, Henderik W.; Osterhaus, Albert D. M. E.; Kuiken, Thijs

doi:10.1128/jvi.06375-11

Cited by 35 publications

(36 citation statements)

References 29 publications

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“…Reperant et al . () also demonstrated that route of infection was important for manifestation and cell tropism. In a recent study (Aamelfot et al .…”

Section: Isa Pathogenesismentioning

confidence: 89%

“…; Toffan, Beato, De Nardi, Bertoli, Salviato, Cattoli, Terregino & Capua ; Klenk ), cats (Reperant et al . ; Rimmelzwaan, van Riel, Baars, Bestebroer, van Amerongen, Fouchier, Osterhaus & Kuiken ) and humans (Korteweg & Gu ; Beutel, Wiesner, Eder, Hafer, Schneider, Kielstein, Kuhn, Heim, Ganzenmuller, Kreipe, Haverich, Tecklenburg, Ganser, Welte & Hoeper ). Reperant et al .…”

Section: Isa Pathogenesisunclassified

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Infectious salmon anaemia – pathogenesis and tropism

Aamelfot

Dale

Falk

2014

Journal of Fish Diseases

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Infectious salmon anaemia (ISA) is a serious disease of farmed Atlantic salmon caused by the aquatic orthomyxovirus infectious salmon anaemia virus (ISAV). ISA was first detected in Norway in 1984 and was characterized by severe anaemia and circulatory disturbances. This review elucidates factors related to the pathogenesis of ISA in Atlantic salmon, the dissemination of the virus in the host and the general distribution of the 4-O-acetylated sialic acids ISAV receptor. The knowledge contributes to the understanding of this disease, and why, almost 30 years after the first detection, it is still causing problems for the aquaculture industry.

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“…Reperant et al . () also demonstrated that route of infection was important for manifestation and cell tropism. In a recent study (Aamelfot et al .…”

Section: Isa Pathogenesismentioning

confidence: 89%

Section: Isa Pathogenesisunclassified

Infectious salmon anaemia – pathogenesis and tropism

Aamelfot

Dale

Falk

2014

Journal of Fish Diseases

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“…Necrosis of the pancreatic ductal epithelium was observed in ferrets intragastrically infected with HP H5N1 virus (30), and pancreatic postmortem lesions ranging from inflammation to necrosis have also been observed in HP-IAV-infected cats (31,32). Pathological examinations of human fatalities from the H1N1 2009 pandemic also revealed pancreatic lesions in two of six postmortem examinations (33), and in our recent studies using in vitro and ex vivo models, we demonstrated that human cells originating from the exocrine pancreas were infected and killed by LP IAVs (34).…”

mentioning

confidence: 99%

Oncolytic Activity of Avian Influenza Virus in Human Pancreatic Ductal Adenocarcinoma Cell Lines

Kasloff

Pizzuto

Silic-Benussi

et al. 2014

J Virol

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Pancreatic ductal adenocarcinoma (PDA) is the most lethal form of human cancer, with dismal survival rates due to late-stage diagnoses and a lack of efficacious therapies. Building on the observation that avian influenza A viruses (IAVs) have a tropism for the pancreas in vivo, the present study was aimed at testing the efficacy of IAVs as oncolytic agents for killing human PDA cell lines. Receptor characterization confirmed that human PDA cell lines express the alpha-2,3-and the alpha-2,6-linked glycan receptor for avian and human IAVs, respectively. PDA cell lines were sensitive to infection by human and avian IAV isolates, which is consistent with this finding. Growth kinetic experiments showed preferential virus replication in PDA cells over that in a nontransformed pancreatic ductal cell line. Finally, at early time points posttreatment, infection with IAVs caused higher levels of apoptosis in PDA cells than gemcitabine and cisplatin, which are the cornerstone of current therapies for PDA. In the BxPC-3 PDA cell line, apoptosis resulted from the engagement of the intrinsic mitochondrial pathway. Importantly, IAVs did not induce apoptosis in nontransformed pancreatic ductal HPDE6 cells. Using a model based on the growth of a PDA cell line as a xenograft in SCID mice, we also show that a slightly pathogenic avian IAV significantly inhibited tumor growth following intratumoral injection. Taken together, these results are the first to suggest that IAVs may hold promise as future agents of oncolytic virotherapy against pancreatic ductal adenocarcinomas. IMPORTANCEDespite intensive studies aimed at designing new therapeutic approaches, PDA still retains the most dismal prognosis among human cancers. In the present study, we provide the first evidence indicating that avian IAVs of low pathogenicity display a tropism for human PDA cells, resulting in viral RNA replication and a potent induction of apoptosis in vitro and antitumor effects in vivo. These results suggest that slightly pathogenic IAVs may prove to be effective for oncolytic virotherapy of PDA and provide grounds for further studies to develop specific and targeted viruses, with the aim of testing their efficacy in clinical contexts.

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“…58 Whether the latter can be infected following ingestion of HPAIV H5N1 is unknown. Such a route of infection has been demonstrated in ferrets, mice, hamsters and cats [35][36][37]107 and implies that these viruses can survive the acidic environment of the stomach in these species.…”

Section: Do Not Distributementioning

confidence: 90%

“…A digestive route of infection is unusual for influenza viruses in humans and other mammals, yet was demonstrated to occur for HPAIV H5N1 in ferrets, mice, hamsters and cats. [35][36][37]107 Similarly to respiratory transmission of avian influenza viruses, such a route of transmission apparently remains highly inefficient, given its relatively low frequency. Lastly, self-inoculation of the conjunctiva appears to be an important and atypical route of bird-to-human transmission of avian influenza viruses of the H7 subtype, which tends to present preferential tropism for ocular tissues in humans.…”

Section: Routes Of Entry and Transmissionmentioning

confidence: 99%