Establishment of HIV-1 model cell line GHOST（3） with stable DRiP78 and NHERF1 knockdown

Chemokine receptors CXCR4 and CCR5 are indispensable co-receptors for HIV-1 entry into host cells. In our previous study, we identified that dopamine receptor-interacting protein 78（DRi P78） and Na＋-H＋ exchanger regulatory factor 1（NHERF1） are the CXCR4 and CCR5 homo- or hetero-dimerinteracting proteins. DRi P78 and NHERF1 are able to influence the co-receptor internalization and intracellular trafficking. Over-expression of NHERF1 affects the ligands or HIV-1 gp120-induced CCR5 internalization and HIV-1 production. It is reasonable to speculate that DRi P78 and NHERF1, as well as the signaling pathways involved in viral replication, would probably affect HIV-1 replication through regulating the co-receptors. In this present study, we designed two short hairpin RNAs（sh RNAs） targeting the DRi P78 and NHERF1, respectively, and constructed the p Lenti6/BLOCK-i T-DEST lentiviral plasmids expressing DRi P78 or NHERF1 sh RNA. The packaged lentiviruses were used to transduce the widely-applied HIV-1 model cell line GHOST（3）. Then, cells with stable knockdown were established through selecting transduced cells with Blasticidin. This study, for the first time, reported the establishment of the GHOST（3） with DRi P78 and NHERF1 knockdown, which is the first stable cell line with HIV-1 co-receptor-interacting molecular defects.

A community-based comprehensive intervention to reduce syphilis infection—among low-fee female sex workers in China:a matched-pair,community-based randomized study

Background:Low-fee female sex workers(FSWs)are at high risk of acquiring and spreading human immunodeficiency virus(HIV)/sexually transmitted diseases(STDs)in China.There is an urgent need to develop comprehensive intervention measures targeted towards low-fee FSWs to reduce HIV/STD infections.Thus,this study aimed to reduce HIV/STD infections among low-fee FSW through a matched-pair,comiDunity-based randomized intervention trial carried out in 12 cities in three provinces in China.Methods:Four cities from Guangxi Zhuang Autonomous Region,four from Yunnan Province,and four from Hunan Province were paired and participants received either the intervention package(including condom promotion,HIV and syphilis testing,reimbursement for syphilis treatment costs,and free anti-retroviral therapy or the current standard of care.Venue-based,convenience sampling was used to recruit FSWs.A face-to-face interview and HIV and syphilis blood testing was conducted at baseline and follow-up intervals of 24 months.Generalized linear mixed models(GLMM)were used to evaluate the effect of the intervention package on reducing HIV/STD infection in the FSWs.Results:A total of 1024 eligible FSWs were enrolled in the baseline survey and 843 in the follow-up.GLMM results showed that syphilis infeaion was reduced by 49%in the intervention group compared to the current standard of care group(P=0.0378,OR=0.51;95%CI:0.27-0.96).FSWs aged 35 years or older were 2.38 times more likely to get syphilis infection compared to those younger than 35 years old(P<0.0001,OR=2.38,95%CI:1.55-3.65).The risk of syphilis infection among more educated FSWs was 0.43 times less than those with lower levels of education(P<0.05,OR=0.43,95%CI:0.63-0.93).Conclusions:This study demonstrates that comprehensive interventions can lead to significant declines in syphilis infection amongst low-tier FSWs.Integrating both behavioral and biomedical intervention measures should be considered when developing programs for low-fee FSWs.Trial registration:CHiCTR-TRC-12002655.