Does apolipoprotein E determine outcome of infection by varicella zoster virus and by Epstein Barr virus?

Over 90% of the population are infected with varicella zoster virus (VZV) but only some develop shingles - caused when the virus reactivates from latency, and only some shingles patients develop post-herpetic neuralgia (PHN), defined as pain continuing for more than about 4 months. Epstein Barr virus (EBV) similarly infects over 90% of the population; some of those infected during teenage or young adult years develop infectious mononucleosis (IM). The reason for these disparities between numbers infected and numbers affected by illness is unknown, but presumably reflects host factor(s). Our previous results showed that apolipoprotein E (APOE) genotype determines susceptibility to, or outcome of, infection in the case of several diseases of known infectious cause. Therefore, we investigated APOE genotypes of shingles, PHN, and IM patients. Our rationale for the previous studies and for investigating VZV was that these micro-organisms use for cell binding and entry the same sites in the cell surface as does the protein apoE, and that consequently, competition with apoE could affect the pathogen's extent of entry and hence extent of the damage caused. The APOE genotypes of shingles and PHN sufferers, and of IM sufferers were determined using restriction fragment length polymorphism. In females, epsilon4 homozygosity confers a risk of shingles and also of IM, and the APOE-epsilon4 allele is protective against PHN whereas APOE-epsilon3 allele is a risk. Our results showing that a host genetic factor influences the development of shingles and PHN in females have clinical significance: they could lead to identification of those (female) patients at greater risk of PHN, thus enabling these people to be targeted for treatment with the most effective drugs.

Learning and retention of associations between auditory icons and denotative referents: implications for the design of auditory warnings.

OBJECTIVE: This study examined the way in which the type and preexisting strength of association between an auditory icon and a warning event affects the ease with which the icon/event pairing can be learned and retained. BACKGROUND: To be effective, an auditory warning must be audible, identifiable, interpretable, and heeded. Warnings consisting of familiar environmental sounds, or auditory icons, have potential to facilitate identification and interpretation. The ease with which pairings between auditory icons and warning events can be learned and retained is likely to depend on the type and strength of the preexisting icon/event association. METHOD: Sixty-three participants each learned eight auditory-icon/denotative-referent pairings and attempted to recall them 4 weeks later. Three icon/denotative-referent association types (direct, related, and unrelated) were employed. Participants rated the strength of the association for each pairing on a 7-point scale. RESULTS: The number of errors made while learning pairings was greater for unrelated than for either related or direct associations, whereas the number of errors made while attempting to recall pairings 4 weeks later was greater for unrelated than for related associations and for related than for direct associations. Irrespective of association type, both learning and retention performance remained at very high levels, provided the strength of the association was rated greater than 5. CONCLUSION: This suggests that strong preexisting associations are used to facilitate learning and retention of icon/denotative-referent pairings. APPLICATION: The practical implication of this study is that auditory icons having either direct or strong, indirect associations with warning events should be preferred.