Summary HIV-1 reverse transcription represents the predominant target for pharmacological inhibition of viral replication, but cell-intrinsic mechanisms that can block HIV-1 reverse transcription in a clinically significant way are poorly defined. We find that effective HIV-1 reverse transcription depends on the phosphorylation of viral reverse transcriptase by host cyclin-dependent kinase (CDK) 2 at a highly conserved Threonin residue. CDK2-dependent phosphorylation increased the efficacy and stability of viral reverse transcriptase and enhanced viral fitness. Interestingly, p21, a cell-intrinsic CDK inhibitor that is upregulated in CD4+ T cells from “elite controllers”, potently inhibited CDK2-dependent phosphorylation of HIV-1 reverse transcriptase and significantly reduced the efficacy of viral reverse transcription. These data suggest that p21 can indirectly block HIV-1 reverse transcription by inhibiting host co-factors supporting HIV-1 replication, and identify sites of viral vulnerability that are effectively targeted in persons with natural control of HIV-1 replication.

Moderately thermophilic bacterial strain CC-HSB-11(T) (Muricauda lutaonensis), which was described recently from a coastal hot spring of Green Island, Taiwan, has been identified to produce zeaxanthin as a predominant xanthophyll by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cell culture in bioreactor produced 3.12 ± 0.18 mg zeaxanthin L(-1) of culture. Micronization of zeaxanthin was achieved through supercritical carbon dioxide antisolvent precipitation method. Yield of zeaxanthin after the process was 53.4%. Dynamic light scattering assay determined the polydisperse existence of micronized particles of size 3 nm to 2 μm. Field emission scanning electron microscopy revealed distinct morphology and size distribution heterogeneity of particles. Integrity of zeaxanthin after the antisolvent process was assessed by LC-MS/MS. The technique capitalizes on the inherent ability of CC-HSB-11(T) to synthesize zeaxanthin and the work demonstrated feasibility of antisolvent precipitation method to produce microparticles exploiting a bacterial strain.

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