The risk of disease associated with persistent virus infections such as HIV-I, hepatitis B and C, and human T-lymphotropic virus-I (HTLV-I) is strongly determined by the virus load. However, it is not known whether a persistent class I HLA-restricted antiviral cytotoxic T lymphocyte (CTL) response reduces viral load and is therefore beneficial or causes tissue damage and contributes to disease pathogenesis. HTLV-I-associated myelopathy (HAM͞TSP) patients have a high virus load compared with asymptomatic HTLV-I carriers. We hypothesized that HLA alleles control HTLV-I provirus load and thus inf luence susceptibility to HAM͞TSP. Here we show that, after infection with HTLV-I, the class I allele HLA-A*02 halves the odds of HAM͞TSP (P < 0.0001), preventing 28% of potential cases of HAM͞TSP. Furthermore, HLA-A*02 ؉ healthy HTLV-I carriers have a proviral load one-third that (P ‫؍‬ 0.014) of HLA-A*02 ؊ HTLV-I carriers. An association of HLA-DRB1*0101 with disease susceptibility also was identified, which doubled the odds of HAM͞TSP in the absence of the protective effect of HLA-A*02. These data have implications for other persistent virus infections in which virus load is associated with prognosis and imply that an efficient antiviral CTL response can reduce virus load and so prevent disease in persistent virus infections.

Tocotrienols are the primary form of vitamin E in seeds of most monocot plants, including cereals such as rice and wheat. As potent antioxidants, tocotrienols contribute to the nutritive value of cereal grains in human and livestock diets. cDNAs encoding homogentisic acid geranylgeranyl transferase (HGGT), which catalyzes the committed step of tocotrienol biosynthesis, were isolated from barley, wheat and rice seeds. Transgenic expression of the barley HGGT in Arabidopsis thaliana leaves resulted in accumulation of tocotrienols, which were absent from leaves of nontransformed plants, and a 10- to 15-fold increase in total vitamin E antioxidants (tocotrienols plus tocopherols). Overexpression of the barley HGGT in corn seeds resulted in an increase in tocotrienol and tocopherol content of as much as six-fold. These results provide insight into the genetic basis for tocotrienol biosynthesis in plants and demonstrate the ability to enhance the antioxidant content of crops by introduction of an enzyme that redirects metabolic flux.

SUMMARY Early life experiences have a major impact on adult phenotypes [1–3]. However, the mechanisms by which animals retain a cellular memory of early experience are not well understood. Here we show that adult wild-type C. elegans that transiently passed through the stress-resistant dauer larval stage exhibit distinct gene expression profiles and life history traits, as compared to adult animals that bypassed this stage. Using chromatin immmunoprecipitation experiments coupled with massively parallel sequencing, we find that genome-wide levels of specific histone tail modifications are markedly altered in post-dauer animals. Mutations in subsets of genes implicated in chromatin remodeling abolish, or alter, the observed changes in gene expression and life history traits in post-dauer animals. Modifications to the epigenome as a consequence of early experience may contribute in part to a memory of early experience, and generate phenotypic variation in an isogenic population.