HIV‑1 Infection Reduces NAD Capping of Host Cell snRNA and snoRNA

Nicotinamide adenine
dinucleotide (NAD) is a critical component
of the cellular metabolism and also serves as an alternative 5′
cap on various RNAs. However, the function of the NAD RNA cap is still
under investigation. We studied NAD capping of RNAs in HIV-1-infected
cells because HIV-1 is responsible for the depletion of the NAD/NADH
cellular pool and causing intracellular pellagra. By applying the
NAD captureSeq protocol to HIV-1-infected and uninfected cells, we
revealed that four snRNAs (e.g., U1) and four snoRNAs lost their NAD
cap when infected with HIV-1. Here, we provide evidence that the presence
of the NAD cap decreases the stability of the U1/HIV-1 pre-mRNA duplex.
Additionally, we demonstrate that reducing the quantity of NAD-capped
RNA by overexpressing the NAD RNA decapping enzyme DXO results in
an increase in HIV-1 infectivity. This suggests that NAD capping is
unfavorable for HIV-1 and plays a role in its infectivity.