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Objective To investigate the expression and function of protein tyrosine phosphatase 4A3(PTP4A3) in terminal erythroid differentiation and underlying molecular mechanism. Methods RT-qPCR was used to detect the expression of Ptp4a3 during terminal differentiation. Knockdown of Ptp4a3 expression in mouse fetal liver induced erythroid differentiation system by short hairpin RNA(shRNA) interference, the knockdown efficiency was verified by RT-qPCR after GFP positive cells were sorted by flow cytometry, and the effect of Ptp4a3 knockdown on erythroid differentiation and enucleation was detected by flow cytometry. Transcriptional profiling was performed to explore the potential downstream pathways of Ptp4a3. Results Ptp4a3 was among the top 100 ranked expressing genes during mouse terminal erythroid differentiation, and its expression gradually increased following the differentiation process. In mouse fetal liver-derived erythroid cells, Ptp4a3 was successfully knocked down by shRNA interference. Flow cytometry analysis showed that Ptp4a3 knockdown significantly decreased the proportion of enucleated erythrocytes(P＜0.05). Transcriptome analysis revealed that Ptp4a3 knockdown resulted in upregulation of cell cycle-related genes. Conclusions PTP4A3 is highly expressed in late stage of terminal erythroid differentiation. Knockdown Ptp4a3 significantly reduces enucleation erythroid of cells.

Men who have sex with men (MSM) have recently accounted for an alarmingly increasing proportion of HIV-1 transmission in China. In order to investigate the immune status as a result of CRF01_AE infection and CXCR4 co-receptor usage in a young Shanghai-based HIV-1-infected MSM population in Shanghai, 364 HIV-1-infected MSM with average age of 22.7 years old, newly diagnosed between Jan 2009 and Jul 2013 were analyzed for CD4+T cell count, subtyping using phylogenetic analysis, and viral co-receptor tropism using Geno2pheno and webPSSM in combination. A total of 276 individuals were identified as recently infected. Subtype assignment were as follows: 176 (63.8%) CRF01_AE, 77 (27.9%) CRF07_BC, and 23 (8.3%) subtype B. Besides, 24 second-generation recombinant strains were identified. A lower CD4+T cell count at baseline survey was observed among CRF01_AE strain-infected individuals, compared to those who were infected with CRF07_BC (P<0.01). The frequency of baseline CD4+T cell count <200 was higher and the frequency of CD4 T counts >500 lower in CRF01_AE infection than CRF07_BC infection. It is worth noting that 32.4%–40.9% of CRF01_AE strain-infected individuals were predicted to carry CXCR4-tropic viruses whereas none of CRF07_BC and subtype B were found to be as CXCR4-tropic viruses (P<0.001). As could be expected CXCR4 tropism was associated with lower CD4 T counts. This study revealed that CRF01_AE strains with high frequency of CXCR4 tropism are prevailing in the young MSM population in China and could potentially cause a severe loss of CD4+T cell count and rapid disease progression. A regular surveillance of HIV-1 subtypes, CD4+T cell count and viral co-receptor usage would be greatly beneficial for effectively monitoring disease progression, improvement of antiretroviral therapy strategy and prompt intervention of transmission. [ABSTRACT FROM AUTHOR]