Antiviral strategies for hepatitis E virus

Abstract

The hepatitis E virus is a common cause of acute hepatitis. Contrary to hepatitis B and C, hepatitis E is mostly a mild infection, although it has a high mortality in pregnant women and can evolve to chronicity in immunocompromised patients. Ribavirin and pegylated interferon-α are the only available therapies, but both have side effects that are not acceptable for prophylaxis or treatment of mild infections. In addition, these drugs cannot be used for all patient types (e.g. in case of pregnancy, specific organ transplants or co-morbidities) and in resource-poor settings. Hence there is an urgent need for better antiviral treatments that are efficacious and safe, also during pregnancy. In this review, a concise introduction to the virus and disease is provided, followed by a discussion of the available assay systems and potential molecular targets (viral proteins and host factors) for the development of inhibitors of HEV replication. Finally, directions for future research are presented.

Antiviral Activities of Different Interferon Types and Subtypes against Hepatitis E Virus Replication

“…3F). Ribavirin monotherapy has been demonstrated to be a successful treatment option for HEV (8) and has been combined with IFN-␣ for decades in HCV therapies. Therefore, we next tested the combinatory antiviral activity of the different IFN-␣ subtypes together with ribavirin.…”

“…The HEV genome is single stranded with an RNA genome size of 7.2 kb (8). The capped positive-sense genome encodes three open reading frames (ORFs): the nonstructural polyprotein required for RNA replication (ORF1), the capsid protein of the HEV virion (ORF2), and a small multifunctional protein with a molecular mass of 13 kDa (ORF3) (9).…”

Rapamycin and everolimus facilitate hepatitis E virus replication: Revealing a basal defense mechanism of PI3K-PKB-mTOR pathway

“…Using a combination of highly potent and well tolerated antivirals, including nucleoside polymerase inhibitors, several studies recently reported a sustained virological response cure in >95% of patients chronically infected with the hepatitis C virus [22]. This latter virus is, akin to HEV, a +ssRNA virus and encodes for several proteins (including a RNA-dependent RNA polymerase) that may be good targets for pharmacological inhibition of viral replication [23]. In fact, it has been shown that some HCV nucleoside polymerase inhibitors (in particular the 2 0 C methyl series) inhibit the replication of yet other +ssRNA viruses including, but not limited to flaviviruses, enteroviruses and noroviruses [24].…”

Épidémiologie de l’hépatite E : une maladie (ré) émergente ?

“…Les génotypes 1 (Asie, Afrique) et 2 (Mexique, Afrique) ont été impliqués dans de grandes épidémies humaines par l'intermédiaire de l'eau et/ou de nourriture contaminées par le VHE dans des pays où les conditions sanitaires sont souvent défectueuses. Le génotype 3 a une distribution mondiale alors que le génotype 4 est plus particulièrement retrouvé en Asie (Chine, Inde, Indonésie, Viêt-Nam, Japon) (figure 1) [4]. Ces deux derniers génotypes sont également responsables d'épidémies humaines dans des pays développés, mais moins sévères et fré-quentes que celles décrites avec les génotypes 1 et 2 (meilleures conditions d'hygiène).…”

“…Ils ont été successivement détectés chez le cochon en 1997 puis chez le poulet et le daim au début des années 2000 [7][8][9][10]. Plus récemment, le VHE a été observé chez le rat, le sanglier, le singe, la mangouste, le lapin, la truite et la chauve-souris (figure 2) [4]. Les porcs infectés par le VHE sont asymptomatiques et ont des lésions histologiques hépatiques le plus souvent minimes [11,12] ; ils excrètent des quantités importantes de VHE dans leurs selles, à l'origine de la contamination d'autres porcs de la même porcherie : le porc constitue ainsi un véritable réservoir du VHE [13].…”