A 35-year-old woman comes to the office due to fever, headache, severe muscle aches, and sore throat for the last 4 days. Physical examination shows mild pharyngeal erythema and nasal congestion. A rapid influenza antigen test is positive. The patient's condition improves over the next several days despite receiving only symptomatic treatment. In response to the influenza virus, infected respiratory epithelial cells begin secreting increased quantities of interferons. The specific interferons secreted by these cells will most likely cause which of the following changes?
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Type I interferons (α and β) are synthesized by most human cells in response to viral infections. Once secreted, α and β interferons bind to type I interferon receptors found on infected and neighboring cells (autocrine/paracrine signaling). This results in transcription of antiviral enzymes capable of halting protein synthesis, such as RNase L (endonuclease that degrades all RNA in the cell) and protein kinase R (inactivates eIF-2, inhibiting translation initiation). However, these enzymes become active only in the presence of double-stranded RNA, which forms in infected cells as a result of viral replication. As a result, normal metabolism and protein synthesis can continue in uninfected cells but is selectively inhibited in virally infected cells.
(Choice A) Interferons α and β induce MHC class I expression on all cells and stimulate the activity of natural killer (NK) and cytotoxic T cells. These processes act to increase the proportion of virally infected cells that undergo apoptosis.
(Choices C and D) Interferon γ is a type II interferon produced mainly by T cells and NK cells. It promotes TH1 differentiation, increases expression of class II MHC molecules on antigen-presenting cells, and improves the intracellular killing ability of macrophages. However, virally infected respiratory epithelial cells would secrete interferons α and β, not interferon γ.
(Choice E) Neutrophils primarily phagocytize and destroy bacterial and fungal pathogens. They do not play a significant role in fighting viral infections, and α and β interferon release by virally infected cells does not promote neutrophil recruitment.
Educational objective:
Interferons α and β are produced by most human cells in response to viral infections. The production of α and β interferons helps suppress viral replication by halting protein synthesis and promoting apoptosis of infected cells, limiting the ability of viruses to spread through the tissues.