IRF7 and RNH1 are modifying factors of HIV-1 reservoirs: a genome-wide association analysis

Background Combination antiretroviral treatment (cART) cannot eradicate HIV-1 from the body due to the establishment of persisting viral reservoirs which are not affected by therapy and reinitiate new rounds of HIV-1 replication after treatment interruption. These HIV-1 reservoirs mainly comprise long-lived resting memory CD4+ T cells and are established early after infection. There is a high variation in the size of these viral reservoirs among virally suppressed individuals. Identification of host factors that contribute to or can explain this observed variation could open avenues for new HIV-1 treatment strategies. Methods In this study, we conducted a genome-wide quantitative trait locus (QTL) analysis to probe functionally relevant genetic variants linked to levels of cell-associated (CA) HIV-1 DNA, CA HIV-1 RNA, and RNA:DNA ratio in CD4+ T cells isolated from blood from a cohort of 207 (Caucasian) people living with HIV-1 (PLHIV) on long-term suppressive antiretroviral treatment (median = 6.6 years). CA HIV-1 DNA and CA HIV-1 RNA levels were measured with corresponding droplet digital PCR (ddPCR) assays, and genotype information of 522,455 single-nucleotide variants was retrieved via the Infinium Global Screening array platform. Results The analysis resulted in one significant association with CA HIV-1 DNA (rs2613996, P < 5 × 10−8) and two suggestive associations with RNA:DNA ratio (rs7113204 and rs7817589, P < 5 × 10−7). Then, we prioritized PTDSS2, IRF7, RNH1, and DEAF1 as potential HIV-1 reservoir modifiers and validated that higher expressions of IRF7 and RNH1 were accompanied by rs7113204-G. Moreover, RNA:DNA ratio, indicating relative HIV-1 transcription activity, was lower in PLHIV carrying this variant. Conclusions The presented data suggests that the amount of CA HIV-1 DNA and RNA:DNA ratio can be influenced through PTDSS2, RNH1, and IRF7 that were anchored by our genome-wide association analysis. Further, these observations reveal potential host genetic factors affecting the size and transcriptional activity of HIV-1 reservoirs and could indicate new targets for HIV-1 therapeutic strategies.

Effects of feeding frequency on growth performances and RNA : DNA ratio of the gangetic mystus (Mystus cavasius Hamilton, 1822) in laboratory condition

Experiments were conducted for a period of 90 days to estimate the effects of different feeding frequencies (one time per day: T1, two times per day: T2, three times per day:T3 and four times per day: T4) on growth performance of gulsha fish reared in laboratory facilities. Significantly higher condition factor was observed in T2 (1.61 ± 0.02) and lowest in T4 (1.40 ± 0.01). Significantly lowest SGR and ADG were recorded in T4 fish fed four times per day. No significant difference was obtained among different treatments for FCR and survival rate. The highest RNA : DNA ratio (0.93 ± 0.07) was observed in fish of T2 and the lowest ratio (0.57 ± 0.11) was observed in fish of T1. The results of the present study suggest that in laboratory rearing two meals per day could be supplied for better growth performances as per indication of condition factor and RNA:DNA ratio. Dhaka Univ. J. Biol. Sci. 27(1): 75-83, 2018 (January)

The effect of photoperiod regimes on daily RNA:DNA ratio rhythms in Chinese soft-shelled turtles (Pelodiscus sinensis)

The ratio of RNA to DNA is widely used to reflect instantaneous animal growth; however, little is known about its daily variation. Photoperiod can modify expression of internal clocks, providing animals with the flexibility to adapt to variable environments. This study focused on the influence of photoperiod regimes on the daily variation of RNA:DNA ratio in Pelodiscus sinensis. We randomly divided 260 turtles into four groups: constant dark (0L), 8 h light with 16 h dark (8L), 12 h light with 12 h dark (12L), and 16 h light with 8 h dark (16L). Turtles were housed under specific photoperiods for 15 days (fed for first 10 days then starved for 5 days), thereafter we sampled the tissues every 2 h for 24 h. We dissected forelimb muscles and measured the concentration of isolated RNA and DNA. There were rhythmic variations in the RNA:DNA ratio, even in turtles under continuous darkness, indicating that P. sinensis has circadian RNA:DNA ratio rhythms, and the rhythms were likely controlled by internal clocks. Additionally, the acrophase was advanced by two hours in constant darkness in contrast to the other three photoperiods, indicating that the photoperiod considerably modified the rhythm set by the internal clocks. Notably, the RNA:DNA ratio differed between photoperiod regimes, with 0L > 16L > 8L ≈ 12L, indicating the photoperiod may be a seasonal indicator for turtles to synchronize their physiological processes with environmental variations.