Identification of interferon-resistant subpopulations in several strains of measles virus: positive selection by growth of the virus in brain tissue

Abstract

Subacute sclerosing panencephalitis (SSPE) is a chronic and usually fatal central nervous system disease caused by a persistent infection with measles virus. The pathogenic mechanisms of the disease are poorly understood, but restricted expression of viral antigens within the infected tissue appears to be involved. We have previously proposed that interferon (IFN) plays a role in the pathogenesis of SSPE by interacting with viral subpopulations that are relatively resistant to IFN-mediated inhibition. Such IFN-resistant viral subpopulations have now been identified in six independent strains of measles virus, two derived from patients with measles and four derived from patients with SSPE. By means of a replicative-plating procedure, these IFN-resistant viruses were found to be heterogeneous with respect to their growth in the presence of high levels of IFN. One viral form replicates fully, with complete destruction of the infected-cell culture, whereas the other form induces a restricted, self-limited form of cytopathic effect, similar to that seen with cell-associated strains of measles virus isolated from SSPE patients. Passage of a virus stock containing both of these viral forms through the central nervous system tissue of newborn hamsters strongly selects for the viral form associated with the self-limiting type of cytopathic effect. The presence of this form of IFN-resistant virus coupled with chronic production of IFN within the central nervous system may account for viral persistence in SSPE patients.

Porcine reproductive and respiratory syndrome virus field isolates differ in in vitro interferon phenotypes

“…Previous experimental work has demonstrated evidence of a relationship between IFN phenotypes and virulence for other viruses. For example, virulent measles virus induces lower levels of IFN than attenuated strains and IFNresistant strains can establish persistent infections of the central nervous system (Carrigan and Knox, 1990). It has also been shown that the capability of noncytopathic bovine viral diarrhea virus to establish persistent infections in the early fetus is related to its ability to suppress type I IFN synthesis (Charleston et al, 2001).…”

Large-population passages of vesicular stomatitis virus in interferon-treated cells select variants of only limited resistance

“…There are several reports of RNA virus proteins with anti-IFN activity (3,24,30,32,38,50). Natural isolates of a particular virus often show variable sensitivity to IFN (4,5,21,23,36,45,46,51), and patients undergoing IFN therapy often show different degrees of responsiveness to the treatment (23,46). Understanding whether and how IFN influences RNA virus evolution is rele-vant to its use in antiviral therapy, especially in the treatment of hepatitis B and C virus and human immunodeficiency virus infections (13,25,35,37).…”

Cell type-specific MxA-mediated inhibition of measles virus transcription in human brain cells

“…This is based on the observation of type I interferon (IFN) in cerebrospinal fluid specimens of patients with persistent central nervous system infections such as subacute sclerosing panencephalitis (SSPE) (13,14,19) and in MV infections of brain cells in tissue culture (16,26,29). In addition, IFN-escape variants have been linked to enhanced neurovirulence in an animal model (4).…”