Friend virus (FV) and lactate dehydrogenase-elevating virus (LDV) are endemic mouse viruses that can cause long-term chronic infections in mice. We found that numerous mouse-passaged FV isolates also contained LDV and that coinfection with LDV delayed FV-specific CD8 ؉ T-cell responses during acute infection. While LDV did not alter the type of acute pathology induced by FV, which was severe splenomegaly caused by erythroproliferation, the immunosuppression mediated by LDV increased both the severity and the duration of

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. abstract: Because of their role in mediating life-history trade-offs, hormones are expected to be strongly associated with components of fitness; however, few studies have examined how natural selection acts on hormonal variation in the wild. In a songbird, the dark-eyed junco (Junco hyemalis), field experiments have shown that exogenous testosterone alters individuals' resolution of the survival-reproduction trade-off, enhancing reproduction at the expense of survival.Here we used standardized injections of gonadotropin-releasing hormone (GnRH) to assay variation in the testosterone production of males. Using measurements of annual survival and reproduction, we found evidence of strong natural selection acting on GnRH-induced increases in testosterone. Opposite to what would be predicted from the survival-reproduction trade-off, patterns of selection via survival and reproduction were remarkably similar. Males with GnRHinduced testosterone production levels that were slightly above the population mean were more likely to survive and also produced more offspring, leading to strong stabilizing selection. Partitioning reproduction into separate components revealed positive directional selection via within-pair siring success and stabilizing selection via extrapair mating success. Our data represent the most complete demonstration of natural selection on hormones via multiple fitness components, and they complement previous experiments to illuminate testosterone's role in the evolution of life-history trade-offs.

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Bateman's principle, which states that male reproductive success should increase with multiple mating, whereas female reproductive success should not, has long been used to explain sex differences in behavior. The statistical relationship between mating success and reproductive success, or Bateman gradient, has been proposed as a way to quantify sex differences in sexual selection. We used a long-term data set on the distribution of paternity in the socially monogamous dark-eyed junco to examine the effect of multiple mating on lifetime reproductive success and to determine the relative contributions of within-pair and extra-pair mating. Both sexes exhibited a strong positive Bateman gradient, even when the number of breeding years was accounted for. Although theory suggests that this pattern indicates a strong potential for sexual selection in both sexes, we argue that the interpretation of strong Bateman gradients, particularly in females, has many potential complications. We discuss several alternative explanations for our results, none of which requires sexual selection acting on female traits, including targeting of inherently fecund females by males seeking extra-pair mates and increased power to detect extra-pair offspring as family size increases. Because neither of these explanations requires that increased mating success causes increased reproductive success, we conclude that using Bateman gradients to measure the potential for sexual selection may be misleading for some mating systems and life histories, such as the iteroparous social monogamy found in juncos.DEPOSIT STATEMENT: This is a pre-copyedited, author-produced PDF of an article accepted for publication in 'Behavioral Ecology' following peer review. The version of record is available online at:10.1093/beheco/ars077.

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Type I IFN play a very important role in immunity against viral infections. Murine type I IFN belongs to a multigene family including 14 IFN-a subtypes but the biological functions of IFN-a subtypes in retroviral infections are unknown. We have used the Friend retrovirus model to determine the anti-viral effects of IFN-a subtypes in vitro and in vivo. IFN-a subtypes a1, a4, a6 or a9 suppressed Friend virus (FV) replication in vitro, but differed greatly in their anti-viral efficacy in vivo. Treatment of FV-infected mice with the IFN-a subtypes a1, a4 or a9, but not a6 led to a significant reduction in viral loads. Decreased splenic viral load after IFN-a1 treatment correlated with an expansion of activated FV-specific CD8 1 T cells and NK cells into the spleen, whereas in IFN-a4-and -a9-treated mice it exclusively correlated with the activation of NK cells. The results demonstrate the distinct anti-retroviral effects of different IFN-a subtypes, which may be relevant for new therapeutic approaches.

The potential roles of TLRs in the cause and pathogenesis of autoimmune CNS inflammation remain contentious. In this study, we examined the effects of targeted deletions of TLR1, TLR2, TLR4, TLR6, TLR9, and MyD88 on the induction of myelin oligodendrocyte glycoprotein 35–55 (MOG35–55) peptide/CFA/pertussis toxin-induced autoimmune encephalomyelitis. Although C57BL/6.Tlr1−/−, C57BL/6.Tlr4−/− and C57BL/6.Tlr6−/− mice showed normal susceptibility to disease, signs were alleviated in female C57BL/6.Tlr2−/− and C57BL/6.Tlr9−/− mice and C57BL/6.Tlr2/9−/− mice of both sexes. C57BL/6.Myd88−/− mice were completely protected. Lower clinical scores were associated with reduced leukocyte infiltrates. These results were confirmed by passive adoptive transfer of disease into female C57BL/6.Tlr2−/− and C57BL/6.Tlr9−/− mice, where protection in the absence of TLR2 was associated with fewer infiltrating CD4+ cells in the CNS, reduced prevalence of detectable circulating IL-6, and increased proportions of central (CD62L+) CD4+CD25+Foxp3+ regulatory T cells. These results provide a potential molecular mechanism for the observed effects of TLR signaling on the severity of autoimmune CNS inflammation.

In many species, each female pairs with a single male for the purpose of rearing offspring, but may also engage in extra-pair copulations. Despite the prevalence of such promiscuity, whether and how multiple mating benefits females remains an open question. Multiple mating is typically thought to be favoured primarily through indirect benefits (i.e. heritable effects on the fitness of offspring). This prediction has been repeatedly tested in a variety of species, but the evidence has been equivocal, perhaps because such studies have focused on pre-reproductive survival rather than lifetime fitness of offspring. Here, we show that in a songbird, the dark-eyed junco ( Junco hyemalis), both male and female offspring produced by extra-pair fertilizations have higher lifetime reproductive success than do offspring sired within the social pair. Furthermore, adult male offspring sired via extra-pair matings are more likely to sire extrapair offspring (EPO) themselves, suggesting that fitness benefits to males accrue primarily through enhanced mating success. By contrast, female EPO benefited primarily through enhanced fecundity. Our results provide strong support for the hypothesis that the evolution of extra-pair mating by females is favoured by indirect benefits and shows that such benefits accrue much later in the offspring's life than previously documented.