Summary auto-generated
This study examined nitric oxide (NO) production during herpes simplex virus type 1 (HSV-1) infection in human U937 monocytic cells. Undifferentiated U937 cells were resistant to HSV-1, but after treatment with phorbol 12-myristate 13-acetate (PMA) to induce differentiation, cells became permissive and produced infectious virus. PMA-differentiated cells infected with HSV-1 produced high levels of NO, comparable to exogenous NO donors. However, when researchers either inhibited NO synthase with L-NMA or added NO donors to enhance NO levels, neither manipulation altered HSV-1 replication rates or cell viability. Despite NO being protective against other viruses in similar systems, it did not affect the course of HSV-1 infection in U937 cells. The authors conclude that while HSV-1 infection induces NO production in differentiated human monocytic cells—the first direct evidence of this—the NO does not play a functional role in modulating the virus infection in vitro.
Key findings
- HSV-1 infection of PMA-differentiated U937 monocytic cells triggers significant nitric oxide production, the first documented evidence of direct NO induction by HSV-1 in human immune cells
- Manipulating NO levels—either reducing it with L-NMA or enhancing it with NO donors—did not alter HSV-1 replication, viral particle production, or cell viability
- Cell differentiation with PMA increased susceptibility to HSV-1 infection through a mechanism independent of nitric oxide, as NO production did not correlate with the increased permissiveness
- Unlike exogenous NO donors shown in prior studies to inhibit HSV-1, the endogenously produced NO appeared ineffective in controlling viral replication
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Abstract
Undifferentiated U937 cells were not susceptible to herpes simplex virus type 1 (HSV-1) infection, but after differentiation with phorbol 12-myristate 13-acetate an increase in the permissivity to the virus was observed accompanied by the production of significant levels of viral particles. High levels of nitric oxide (NO) were produced in differentiated U937 cells infected with HSV-1. This production was comparable to that observed after addition of the NO donor glycerine trinitrate. The levels of NO drastically decreased when the cells were incubated with L-monomethyl arginine (L-NMA), an inhibitor of NO synthase. Although similar levels of NO were sufficient to decrease susceptibility of U937 cells to other viruses, neither incubation with NO donors nor addition of L-NMA altered the permissiveness to HSV-1 infection. Thus, these results suggest that NO does not interfere with the replication of HSV-1 in U937 cells.