Early biochemical studies of viral replication suggested that most viruses produce
double-stranded RNA (dsRNA), which is essential for the induction of the host immune response. However, it was reported in 2006 that dsRNA could be detected by immunofluorescence antibody staining in
double-stranded DNA and positive-strand RNA virus
infections but not in negative-strand
RNA virus infections. Other reports in the literature seemed to support these observations. This suggested that negative-strand RNA viruses produce little, if any, dsRNA or that more efficient viral countermeasures to mask dsRNA are mounted. Because of our interest in the use of dsRNA
antibodies for virus discovery, particularly in pathological specimens, we wanted to determine how universal immunostaining for dsRNA might be in animal virus
infections. We have detected the in situ formation of dsRNA in cells infected with
vesicular stomatitis virus, measles virus, influenza A virus, and Nyamanini virus, which represent viruses from different negative-strand RNA virus families. dsRNA was also detected in cells infected with lymphocytic choriomeningitis virus, an ambisense RNA virus, and minute virus of mice (MVM), a
single-stranded DNA (ssDNA) parvovirus, but not hepatitis B virus. Although dsRNA staining was primarily observed in the cytoplasm, it was also seen in the nucleus of cells infected with influenza A virus, Nyamanini virus, and MVM. Thus, it is likely that most animal virus
infections produce dsRNA species that can be detected by immunofluorescence staining. The apoptosis induced in several uninfected cell lines failed to upregulate dsRNA formation.
IMPORTANCE: An effective
antiviral host immune response depends on recognition of viral invasion and an intact innate immune system as a first line of defense.
Double-stranded RNA (dsRNA) is a viral product essential for the induction of innate immunity, leading to the production of
type I interferons (IFNs) and the activation of hundreds of IFN-stimulated genes. The present study demonstrates that
infections, including those by ssDNA viruses and positive- and negative-strand RNA viruses, produce dsRNAs detectable by standard immunofluorescence staining. While dsRNA staining was primarily observed in the cytoplasm, nuclear staining was also present in some
RNA and
DNA virus infections. The nucleus is unlikely to have
pathogen-associated molecular pattern (
PAMP) receptors for dsRNA because of the presence of host dsRNA molecules. Thus, it is likely that most animal virus
infections produce dsRNA species detectable by immunofluorescence staining, which may prove useful in viral discovery as well.