Subviral Dense Bodies of Human Cytomegalovirus Enhance Interferon-Beta Responses in Infected Cells and Impair Progeny Production.

(1)

Background

Infection with human cytomegalovirus (HCMV) leads to the production and release of subviral particles, termed Dense Bodies (DB). They are enclosed by a membrane resembling the viral envelope. This membrane mediates the entrance of DBs into cells in a way that is comparable to virus infection. HCMV attachment and entry trigger the induction of interferon synthesis and secretion, and the subsequent expression of interferon-regulated genes (IRGs) that might inhibit replication of the virus. Recently, we demonstrated that DBs induce a robust interferon response in the absence of infection. Little is known thus far, including how DBs influence HCMV infection and virus-host interaction. (2)

Methods

Purified DBs were used to study the impact on virus replication and on the innate defense mechanisms of the cell. (3)

Results

The incubation of cells with DBs at the time of infection had little effect on viral genome replication. Preincubation of DBs, however, led to a marked reduction in viral release from infected cells. These cells showed an enhancement of the cytopathic effect, associated with a moderate increase in early apoptosis. Despite virus-induced mechanisms to limit the interferon response, the induction of interferon-regulated genes (IRGs) was upregulated by DB treatment. (4)

Conclusions

DBs sensitize cells against viral infection, comparable to the effects of interferons. The activities of these particles need to be considered when studying viral-host interaction.