Perinuclear accumulation of hepatitis a virus proteins, RNA, and particles and ultrastructural alterations in infected cells

The exact intracellular site of hepatitis A virus (HAV) production is unknown, possibly due to its usually slow and inefficient replication. Using immunocytochemistry and in-situ RT-PCR, we show that in cells infected with the rapidly replicating HAV strain HAS-15, viral proteins and RNA are scattered throughout the cytoplasm and accumulate in the perinuclear cytoplasmic area. Various ultrastructural alterations were found in infected cells, such as large polyribosomes, swelling of the perinuclear space and the ER, and dilatation of Golgi cisternae. In addition, HAV infection induced the formation of large arrays of annulate lamellae. Direct visualization of HAV particles was scarce. The various ultrastructural alterations described here might represent different phases of the replicative cycle of HAV that is asynchronous in the infected cell layer.