Experimental manipulation of population-level MHC diversity controls pathogen virulence evolution in Mus musculus.

The virulence levels attained by serial passage of pathogens through similar host genotypes are much higher than observed in natural systems; however, it is unknown what keeps natural virulence levels below these empirically demonstrated maximum levels. One hypothesis suggests that host diversity impedes pathogen virulence, because adaptation to one host genotype carries trade-offs in the ability to replicate and cause disease in other host genotypes. To test this hypothesis, with the simplest level of population diversity within the loci of the major histocompatibility complex (MHC), we serially passaged Friend virus complex (FVC) through two rounds, in hosts with either the same MHC genotypes (pure passage) or hosts with different MHC genotypes (alternated passage). Alternated passages showed a significant overall reduction in viral titre (31%) and virulence (54%) when compared to pure passages. Furthermore, a resistant host genotype initially dominated any effects due to MHC diversity; however, when FVC was allowed to adapt to the resistant host genotype, predicted MHC effects emerged; that is, alternated lines show reduced virulence. These data indicate serial exposure to diverse MHC genotypes is an impediment to pathogen adaptation, suggesting genetic variation at MHC loci is important for limiting virulence in a rapidly evolving pathogen and supports negative frequency-dependent selection as a force maintaining MHC diversity in host populations.

The olfactory loss that accompanies an HIV infection.

A number of studies have shown that HIV infection is associated with decreased olfactory ability. Additionally, it has been hypothesized that a reduced odorant identification may precede the advent of AIDS Dementia Complex (ADC). However, it is not known whether changes in olfactory ability are a manifestation of neurocognitive decline which may precede the appearance of AIDS Dementia Complex, damage to the peripheral olfactory system from opportunistic infection, or whether olfactory structures have a particular sensitivity to HIV. These issues were addressed in a cross-sectional study examining variability in the neuropsychological, neurological, otolaryngological, auditory, and olfactory status in HIV-positive subjects. A stepwise regression provided evidence that the ability to identify odorants was influenced by age, nasal structure and pathology, neurocognitive ability, and level of AIDS Dementia Complex. On the other hand, only nasal pathologies accounted for the variability in olfactory thresholds. These data suggest that identification and thresholds tests may reflect different olfactory pathologies. Additionally, these data suggest at least part of the decline in olfactory ability accompanying an HIV infection may be secondary to nasal pathologies. Because of their rapidly changing neurocognitive status, HIV-positive patients represent an excellent group in which to study the determinants of olfactory ability.