Macrophage Depletion Reactivates Fecal Virus Shedding following Resolution of Acute Hepatitis A inIfnar1^–/–Mice

Abstract

HAV RNA persists in the liver of infected chimpanzees and interferon receptor-deficient Ifnar1 −/− mice for many months after neutralizing antibodies appear, virus has been cleared from the blood, and fecal virus shedding has terminated. Here, we show this viral RNA is located within hepatocytes and that the depletion of macrophages months after the resolution of hepatic inflammation restores fecal virus shedding and circulating viral RNA.

Recent advances in hepatitis A virus research and clinical practice guidelines for hepatitis A virus infection in Japan

“…21,23,24,227 Interferon and cytokine signaling play a role in inhibition of HAV replication. 211,216,[228][229][230][231][232] Ultrastructural alterations were observed in HAV-infected cells, such as large polyribosomes, swelling of the perinuclear space and the endoplasmic reticulum, and dilatation of Golgi cisternae. 233 Glucose-regulated protein 78, which is a chaperone protein and orchestrates the unfolded protein response in the endoplasmic reticulum, is involved in regulation of HAV replication.…”

“…Cleavage of mitochondrial antiviral signaling by HAV 3ABC protease boosts viral replication and promotes disease pathogenesis, and HAV protease inhibitors suppress these reactions, as well as cleaving HAV polyproteins, resulting in inhibition of HAV replication 21,23,24,227 . Interferon and cytokine signaling play a role in inhibition of HAV replication 211,216,228–232 . Ultrastructural alterations were observed in HAV‐infected cells, such as large polyribosomes, swelling of the perinuclear space and the endoplasmic reticulum, and dilatation of Golgi cisternae 233 .…”