RSV Protects Itself From Programmed Cell Death
abstract & commentary
Synopsis: Some viruses are cleared through apoptosis, but there are viral-induced mechanisms to thwart the programmed cell death.
Source: Krilov LR, et al. Alterations in apoptosis of cord and adult peripheral blood mononuclear cells induced by in vitro infection with respiratory syncytial virus. J Infect Dis 2000; 181:349-353.
The understanding of apoptosis is gaining importance in many fields of medicine, particularly infectious diseases. Journals are now dedicated to the process that features programmed cell death related to normal tissue turnover and to immune-induced factors. It is usually hard to determine if apoptosis in a given disease is good or bad for humans. In general, apoptosis is a protective process, then in viral illnesses the process could be viewed as a way to remove, for example, virus-infected cells. Certain viruses, conversely, have evolved mechanisms for blocking apoptosis.
Respiratory syncytial virus (RSV) is gaining importance in adult as well as pediatric infections. In this report, workers at North Shore University Hospital and NYU School of Medicine took peripheral blood mononuclear cells (PBMCs), either cord blood PBMCs from infants or adults, and exposed them to RSV. Apoptosis was blunted in PBMCs, including specific lymphocyte populations (B, T, and NK cells), and macrophages. The effect was more pronounced in adult blood than in cord blood.
Comment by Joseph F. John, md
It is thought that the pathogenesis of RSV relates to host responses increasing reactivity of airways. RSV is known to infect macrophages and monocytes in vitro, so impairment of apoptosis in these cells’ lines was predictable. The decrease of apoptosis in lymphocytes may be less related to direct infection than to cytokine-mediated processes.
The industry is working hard to develop molecules that interact with apoptosis mechanisms. It will not be surprising to see imminent development of a compound that could promote normal apoptosis in non-immunosuppressed patients infected with RSV. On the other hand, this study raises the issue of an additional mechanism by which RSV affects neutropenic patients such as those in bone marrow units, who have a catastrophic response to this virus. Perhaps direct infection of non-PBMC cells plays a larger role in neutropenic patients.
What is the role of apoptosis in RSV infected macrophages?
a. RSV induces apoptosis
b. RSV has no effect on apoptosis
c. RSV inhibits apoptosis
d. RSV stimulates cytokine production by macrophages that reduce macrophage viability
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