Hematite Hollow-Sphere-Array Photoanodes for Efficient Photoelectrochemical Water Splitting.

Constructing 3D nanophotonic structures is regarded as an effective method to realize efficient solar-to-hydrogen conversion. These photonic structures can enhance the absorbance of photoelectrodes by the light trapping effect, promote the charge separation by designable charge transport pathway and provide a high specific surface area for catalytic reaction. However, most 3D structures reported so far mainly focused on the influence of light absorption and lacked a systematic investigation of the overall water splitting process. Herein, hematite hollow-sphere-array photoanodes are fabricated through a facile hydrothermal method with polystyrene templates. Validating by simulations and experiments, the hollow sphere array is proved to enhance the efficiency of light harvesting, charge separation and surface reaction at the same time. With an additional annealing treatment in oxygen, a photocurrent density of 2.26 mA cm-2 at 1.23 V versus reversible hydrogen electrode can be obtained, which is 3.70 times larger than that with a planar structure in otherwise the same system. This work gains an insight into the photoelectrochemical water splitting process, which is valuable for the further design of advancing solar driven water splitting devices.

HAMdetector: a Bayesian regression model that integrates information to detect HLA-associated mutations.

MOTIVATION: A key process in anti-viral adaptive immunity is that the human leukocyte antigen (HLA) system presents epitopes as major histocompatibility complex I (MHC I) protein-peptide complexes on cell surfaces and in this way alerts CD8+ cytotoxic T-lymphocytes (CTLs). This pathway exerts strong selection pressure on viruses, favoring viral mutants that escape recognition by the HLA/CTL system. Naturally, such immune escape mutations often emerge in highly variable viruses, e.g. HIV or HBV, as HLA-associated mutations (HAMs), specific to the hosts MHC I proteins. The reliable identification of HAMs is not only important for understanding viral genomes and their evolution, but it also impacts the development of broadly effective anti-viral treatments and vaccines against variable viruses. By their very nature, HAMs are amenable to detection by statistical methods in paired sequence/HLA data. However, HLA alleles are very polymorphic in the human host population which makes the available data relatively sparse and noisy. Under these circumstances, one way to optimize HAM detection is to integrate all relevant information in a coherent model. Bayesian inference offers a principled approach to achieve this. RESULTS: We present a new Bayesian regression model for the detection of HAMs that integrates a sparsity-inducing prior, epitope predictions and phylogenetic bias assessment, and that yields easily interpretable quantitative information on HAM candidates. The model predicts experimentally confirmed HAMs as having high posterior probabilities, and it performs well in comparison to state-of-the-art models for several datasets from individuals infected with HBV, HDV and HIV. AVAILABILITY AND IMPLEMENTATION: The source code of this software is available at https://github.com/HAMdetector/Escape.jl under a permissive MIT license. The data underlying this article were provided by permission. Data will be shared on request to the corresponding author with permission of the respective co-authors. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The first third-generation HIV-1 circulating recombinant form (CRF114_0155) identified in central China.

A novel circulating recombinant form (CRF) was identified in eight HIV-1-infected patients without direct epidemiological relationships in Henan Province, Central China. Recombination analysis indicated that the genome of this novel CRF comprises five segments: three inherited from CRF01_AE cluster-4 and two from CRF55_01B. Therefore, the CRF was designated CRF114_0155. It is not only the first novel CRF identified in Henan Province but also the first third-generation CRF of HIV-1 and the first CRF descendant of CRF55_01B. Bayesian inference of phylogeny dated the most recent common ancestor of the CRF114_0155 cluster to 2010. The emergence of CRF114_0155 reflects that the genotype constitution of HIV-1 has become more complex and that stricter intervention measures should be implemented in central China.

Variations in Env at amino acids 328 and 330 affect HIV-1 replicative fitness and entry inhibitor sensitivity.

While the variations in the HIV-1 Env V3 loop have been the focus of much research to explore its functional effect, how specific mutations of certain amino acids in the V3 loop affect viral fitness remains unclear. In this study, we evaluated a series of natural polymorphisms at positions 328 and 330 with different combinations of adjacent glycosylation sites in the HIV-1 subtype B backbone to address their role in replicative fitness and sensitivity to entry inhibitors based on analysis of env sequence frequency at the population level. Pairwise growth competition experiment showed that wild-type virus with major consensus amino acids obviously had higher replicative fitness (P < 0.001). A change at position 328 to a less frequently occurring amino acid, K, together with a mutated N332 glycosylation site harbored lower fitness and became more sensitive to coreceptor antagonists (AMD3100), fusion inhibitors (T20) and sCD4. A change at position 330 to a less frequently occurring amino acid, Y, together with a mutated N332 glycosylation site resulted in higher fitness and less sensitivity to entry inhibitors (T20, AMD3100, and sCD4), and viruses containing both changes showed intermediate activity. It seems that the H330Y mutation compensated for the reduced replicative capacity caused by the Q328 K mutation. Moreover, viruses that showed lower replicative fitness also exhibited slower entry kinetics, lower levels of replication intermediates and protein packaging, and a lower ability to replicate in primary peripheral blood mononuclear cells (PBMCs). The findings highlight the functional effect of variations at 328 and 330 in the V3 loop on replicative fitness and may benefit HIV-1 treatment by helping predict the sensitivity to entry inhibitors.

Genetic Diversity, Complicated Recombination, and Deteriorating Drug Resistance Among HIV-1-Infected Individuals in Wuhan, China.

To identify genotype distribution and drug resistance in people infected by HIV-1 in Wuhan, China, 105 infected people diagnosed with HIV-1 from January to December in 2019 were involved in this study. Ninety-eight gag genes, 101 PR genes, and 98 RT genes were successfully amplified. The phylogenetic analysis results showed that CRF01_AE (38.2%) and CRF07_BC (35.3%) were the two dominant genotypes, followed by CRF55_01B (6.9%), CRF59_01B (2.0%), B (2.0%), B' (2.0%), CRF08_BC (1.0%), CRF80_0107 (1.0%), and unique recombinant form (URF) (11.8%). Most URFs were the recombinants between CRF01_AE and CRF07_BC or CRF07_BC and CRF55_01B. Among the 93 subjects of antiretroviral therapy (ART)-naive, transmitted drug resistance against non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 23.9%, of which V179D/E was the most frequent mutation, accounting for 18.2%. Among the 12 subjects of ART-experienced, drug resistance to first-line regimens developed severely.

Evaluation of susceptibility of HIV-1 CRF01_AE variants to neutralization by a panel of broadly neutralizing antibodies.

Broadly neutralizing antibodies (bNAbs) are very promising agents for HIV-1 prophylaxis and AIDS treatment. However, the neutralization susceptibility of circulating recombinants such as CRF01_AE, which is becoming increasingly prevalent, has not been studied in detail until now. Here, we focused on CRF01_AE in China and aimed to find bNAbs that can be used for neutralization of CRF01_AE. Full-length env clones were obtained from the plasma samples of 22 HIV-1-infected individuals sampled in 2009 and 2015. An env-pseudovirus-based neutralization assay was conducted using five categories of bNAbs: VRC01, NIH45-46G54W, and 3BNC117 (targeting the CD4 binding site); PG9 and PG16 (targeting the V1V2 loop); 2G12 (glycan specific), PGT121 and 10-1074 (targeting the V3 glycan); 2F5, 4E10, and 10E8 (targeting the membrane-proximal external region (MPER)). The neutralizing efficiency was compared, and features of the escape pseudoviruses were analyzed. The CRF01_AE pseudoviruses exhibited different susceptibility to these bNAbs. Overall, 4E10, 10E8, and 3BNC117 neutralized all 22 env-pseudotyped viruses, followed by NIH45-46G54W and VRC01, which neutralized more than 90% of the viruses. 2F5, PG9, and PG16 showed only moderate breadth, while the other three bNAbs neutralized none of these pseudoviruses. Specifically, 10E8, NIH45-46G54Wand 3BNC117 showed the highest efficiency, combining neutralization potency and breadth. Mutations at position 160, 169, 171 were associated with resistance to PG9 and PG16, while loss of a potential glycan at position 332 conferred insensitivity to V3-glycan-targeting bNAbs. Our results may help for choosing bNAbs that can be used preferentially for prophylactic or therapeutic approaches in China.

Surveillance of HIV-1 drug resistance in Xinjiang: high prevalence of K103N in treatment-naïve individuals.

To identify transmitted and acquired HIV-1 drug resistance mutations in Xinjiang, China, we collected the peripheral blood of 50 treated and 50 treatment-naïve HIV-1-infected individuals in this region. We successfully amplified 36 reverse transcriptase and 42 protease gene sequences of HIV-1 from 51 individuals and identified mutations associated with resistance to reverse transcriptase (RT) and protease (PR) inhibitors (RTIs and PIs) according to Stanford Drug Resistance Database. Among the drug-treated individuals, the results showed that K103N in the RT region was the most frequent mutation, found in 67% (6/9) of the cases, followed by M184V with 56% (5/9). Five individuals had both nucleoside and non-nucleoside reverse transcriptase inhibitor resistance mutations after more than 12 months of treatment. Among the untreated individuals, 33% (9/27) were found to harbor drug resistance mutations in the RT gene. K103N occurred at the highest rate, accounting for 22% (6/27), followed by P225H (7%) and Y188L (4%). Neither of the two groups showed any major resistance mutations to PIs. Our study revealed that the prevalence of drug resistance was relatively high in Xinjiang and that K103N occurred at the highest rate. These results suggest that it is important to carry out HIV drug resistance testing, especially for the K103N mutation in the RT region, before and during the treatment process. This study may help to guide ART strategies in the Xinjiang region.

DCAF1 is involved in HCV replication through regulation of miR-122.

Hepatitis C virus (HCV) is a worldwide threaten to human health with a high ratio of chronic infections. Recently, we found that Vpr-mediated regulation of HCV replication depends on the host protein DDB1-Cul4 associate factor 1 (DCAF1), implying that DCAF1 might be involved in the replication of HCV. In this study, we demonstrated that DCAF1 knockdown reduced HCV replication both in the infectious (JFH1) and replicon (Con1) systems. Further investigation showed a negative regulation of HCV internal ribosome entry site (IRES)-mediated translation by DCAF1. Considering the positive effects on the replication of the HCV replicon, we speculated that DCAF1 affected the balance between HCV RNA replication and protein translation. Since miR-122 is involved in the regulation of this balance, we investigated the influence of DCAF1 on miR-122 expression. By measuring the expression of miR-122, pre-miR-122 and its target CAT-1 mRNA, we found that miR-122 was downregulated following DCAF1 knockdown. Furthermore, overexpression of miR-122 rescued HCV replication impairment induced by DCAF1 knockdown. In conclusion, our study suggests that DCAF1 is involved in HCV replication through regulation of miR-122 and thus provides new insights into the interaction between HCV and the host cell.

Expression Pattern of Individual IFNA Subtypes in Chronic HIV Infection.

Interferon-α (IFN-α) plays an important role in HIV pathogenesis. IFN-α consists of 13 individual IFN-α subtypes, which exhibit individual antiviral and immunomodulatory activities in HIV infection. Here, we determined the expression profiles of all IFN-α subtypes in treated and treatment-naive HIV+ patients and their impact on the induction of distinct HIV restriction factors. We collected blood samples of chronic HIV+ patients, which underwent antiretroviral therapy or were treatment-naive, and determined the individual expression levels of different IFN-α subtypes and HIV restriction factors. HIV infection transiently enhanced the expression of IFNA mRNA. The IFN-α response was dominated by the most abundantly expressed subtypes IFNA4, A5, A7, and A14 in all individuals. HIV infection affected the expression pattern of the IFN-α response, in particular for IFNA2 and IFNA16, which were elevated by chronic HIV infection. Elevated expression of HIV restriction factors was observed in chronically HIV-infected patients, which partly decreased during successful antiretroviral treatment. In vitro stimulation of peripheral blood mononuclear cells revealed that IFN-α6, -α14, and -α21 were most effective in inducing the expression of HIV restriction factors. These results indicate that HIV infection induces a specific expression pattern of IFN-α subtypes, which in turn induce the expression of various HIV restriction factors.

Drug resistance mutation profiles of the drug-naïve and first-line regimen-treated HIV-1-infected population of Suzhou, China.

Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance (TDR) and acquired drug resistance mutation (ADR) profiles, we collected blood specimens from 127 drug-naïve and 117 first-line drug-treated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified pol fragments from 100 drug-naïve and 20 drug-treated samples. We then determined the drug-resistant mutations to protease (PR) and reverse-transcriptase (RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted (drug-naïve group) and acquired (treated group) resistance mutations, respectively. Six transmitted drug-resistant mutations were found, including two mutations (L33F and L76V) in the protease region and four (K70N/E and V179D/E) in the RT region. Only L76V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.

Phylodynamics of major CRF01_AE epidemic clusters circulating in mainland of China.

As the most dominant HIV-1 strain in China, CRF01_AE needs to have its evolutionary and demographic history documented. In this study, we provide phylogenetic analysis of all CRF01_AE pol sequences identified in mainland China. CRF01_AE sequences were collected from the Los Alamos HIV Sequence Database and the local Chinese provincial centers of disease control and prevention. Phylogenetic trees were constructed to identify major epidemic clusters. Bayesian coalescent-based method was used to reconstruct the time scale and demographic history. There were 2965 CRF01_AE sequences from 24 Chinese provinces that were collected, and 5 major epidemic clusters containing 85% of the total CRF01_AE sequences were identified. Every cluster contains sequences from more than 10 provinces with 1 or 2 dominant transmission routes. One cluster arose in the 1990s and 4 clusters arose in the 2000s. Cluster I is in the decline stage, while the other clusters are in the stable stage. Obvious lineage can be observed among sequences from the same transmission route but not the same area. Two large clusters in high-level prevalence were found in MSM (Men who have sex with men), which highlighted that more emphasis should be placed on MSM for HIV control in mainland China.

The Changes of Positive Selection Within env Gene of HIV-1 B', CRF07_BC and CRF08_BC from China Over Time.

BACKGROUND: It is not clear about the possible evolutionary changes of the three predominant strains of HIV-1 in China over the course of the epidemic. Envelope (env) gene of HIV-1 is a good target for this evolutionary pressure for its enriched epitopes. METHODS: We collected 159 full or part of env sequences sampled between 1997 and 2010 from database of China, we calculated the genetic distance, detected the positively selected sites by PAML suite and then compared the number using Fisher's exact test between the early period 1997 to 2003 and the late period 2004 to 2010. RESULTS: We found that the diversity of env genes had increased significantly and the positively selected sites were significantly becoming more over time. V2, V4, and C3 regions had suffered an increase positive selection pressure, while V1, V3, V5 and other conserved regions were relatively stable. Several sites were widely selected and compactly located in C3 and V4, five sites were consecutive in V4.There were two common positively selected sites in all groups: 413T in gp120 and 619L in gp41. CONCLUSION AND DISCUSSION: The common positively selected sites identified in our study implied that they are important in viral survival and adaptation. Based on the role of V3 region in coreceptor determination and disease progression, our results suggested that the virulence of HIV-1 in China might be stable in the short time span. Given the overall increased tendency of positively selection sites in env, we might predict a less virulent state in the long run.

An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating.

BACKGROUND: Several members of the TRIM family have been implicated in antiviral defense. Our previous report showed that human TRIM11 potently inhibited HIV-1 transduction by reducing the viral reverse transcripts. These results prompted us to examine the effect of TRIM11 on HIV-1 uncoating, which is closely related to viral reverse transcription. RESULTS: Using a combination of in vitro binding and in situ proximity ligation assay, we showed that TRIM11 could interact with HIV-1 capsid. Overexpression of TRIM11 accelerates HIV-1 uncoating and reduces viral reverse transcription indicated by the fate-of-capsid assay and quantitative PCR respectively. Knockdown of TRIM11 enhanced HIV-1 capsid stability and increased viral reverse transcription. However, the replication of another retrovirus MLV is not affected by TRIM11. Moreover, the reverse transcription of HIV-1 mutant bearing capsid G89V showed insensitivity to restriction by TRIM11, indicating that the viral determinant of restriction by TRIM11 might reside on capsid. Using microtubule dynamics inhibitors, we revealed that microtubule dynamics contributes to TRIM11-mediated HIV-1 capsid premature disassembly and the reduction of reverse transcription levels. Finally, we demonstrated that TRIM11 inhibits HIV-1 transduction and accelerates viral uncoating in HIV-1 permissive THP-1-derived macrophages. CONCLUSIONS: We identify TRIM11 as a new HIV-1 capsid binding protein. Our data also reveal that TRIM11 restricts HIV-1 reverse transcription by accelerating viral uncoating, and microtubule dynamics is implicated in TRIM11-imposed block to early events of HIV-1 replication.

Ficolin-2 binds to HIV-1 gp120 and blocks viral infection.

Ficolin-2 is a lectin complement pathway activator present in normal human plasma and usually associated with infectious diseases, but little is known about the role of ficolin-2 in human immunodeficiency virus (HIV) infection. Here, we describe our novel findings that serum ficolin-2 concentrations of 103 HIV-1 patients were much higher compared to those of 57 healthy donors. In vitro analysis showed that HIV-1 infection could enhance ficolin-2 expression. We further demonstrated that recombinant ficolin-2 protein could bind with HIV-1 envelope glycoprotein gp120, and subsequently induce complement dependent cytotoxicity. Moreover, ficolin-2 could block the entry of HIV-1 into target cells (TZM-b1 and MT-2 cells) and infection in a ficolin-2 dosedependent manner. To our knowledge, this is the first report about the protective role of ficolin-2 against HIV-1 infection and our study suggests that ficolin-2 is an important human innate immune molecule against HIV.

[Upregulated PD-1 on CD8+T cells is positively correlated with activation of T cells during HIV-1 infection].

Objective To investigate the expressions of programmed death-1 (PD-1), CD38, human leukocyte antigen DR (HLA-DR) and anligen KI-67(ki67) on CD8+ T cells, and the correlation between PD-1/PD-L1 pathway and activation, immunodepletion during HIV-1 infection. Methods Peripheral blood mononuclear cells were isolated by density gradient centrifugation from 87 HIV-1 patients and 22 healthy controls. The expression levels of PD-1, CD38, HLA-DR and ki67 on CD8+T cells were detected by flow cytometry. Furthermore, we evaluated the production of interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) in CD8+ T cells by blocking PD-1/PD-L1 pathway in the presence of PD-L1 mAb. Results Compared with healthy controls, HIV-1 infection resulted in a significant increase in PD-1 expression on CD8+T cells. Correlation analysis showed that PD-1 expression on CD8+T cell was positively associated with HIV-1 viral loading (VL) and negatively associated with the number of CD4+T cells. Furthermore, PD-1 expression was positively correlated with CD38 and HLA-DR expressions on CD8+T cells in HIV-1 infected patients. There was no association between PD-1 and ki67 expression on CD8+T cells in HIV-1 infected patients. Blockage of the PD-1/PD-L1 pathway increased TNF-α and IFN-γ production in CD8+T cells. Conclusion PD-1 expression on CD8+T cells is significantly upregulated during HIV-1 infection. PD-1 expression is correlated with CD8+T cell inhibition, immunodepletion and disease progression. Moreover, the blockage of PD-1/PD-L1 pathway can restore the function of CD8+T cells in HIV-1 patients.

Roles of microRNAs in HIV-1 Replication and Latency.

MicroRNAs (miRNAs) are non-coding RNA molecules, with sequence length of 19-24 nucleotides, which can induce mRNA degradation and regulate protein translation repression. Recently plenty of reports showed that miRNAs increase or decrease in the serum (circulating miRNAs) and in PBMC of Human immunodeficiency virus type 1 (HIV-1) infected individuals to affect the replication of HIV-1 through regulating HIV-1 proteins or HIV-1 replication related host factors. Many of miRNAs can suppress HIV-1 replication, but do not affect the integrated viral DNA. Low or no viral protein expression could result in a block of virus and its replication to induce HIV-1 latency, which is the great obstacle of the cure of HIV-1 infection. In the HIV-1 latency reservoir, the integrated provirus can reactivate under appropriate stimulus, which results in HIV-1 reproduction. Factors imply that cellular miRNAs may promote the establishment of HIV-1 latency. Further studies on the mechanisms of miRNAs affecting viral protein expression will provide new approaches to clear the viral reservoir.

HIV-1 Vpr increases HCV replication through VprBP in cell culture.

Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs at a high frequency, in which HIV shows a promotion of HCV-derived liver diseases. However, the mechanism of how this occurs is not well understood. Our previous work has demonstrated that the HIV-1 accessory protein Vpr enhances HCV RNA replication in cell culture. Because Vpr performs most of its functions through host protein VprBP (DCAF1), the role of VprBP in the regulation of HCV by Vpr was investigated in this study. We found that the Vpr mutant Q65R, which is deficient in VprBP binding, could not enhance HCV replication. Furthermore, Vpr-mediated enhancement of HCV replication was severely diminished in VprBP knockdown cells. In addition, an inhibitor of Cullin RING E3 ligases, MLN4924, impaired the function of Vpr during HCV replication. Together, these results suggest that Vpr promotes HCV replication in a VprBP-dependent manner, and that the activity of Cullin RING E3 ligases is essential to this process. In conclusion, our findings demonstrate that HIV-1 Vpr makes the cellular environment more suitable for HCV replication, which might relate with the host ubiquitination system.

The V1 region of gp120 is preferentially selected during SIV/HIV transmission and is indispensable for envelope function and virus infection.

A transmission bottleneck occurs during each human immunodeficiency virus (HIV) transmission event, which allows only a few viruses to establish new infection. However, the genetic characteristics of the transmitted viruses that are preferentially selected have not been fully elucidated. Here, we analyzed amino acids changes in the envelope protein during simian immunodeficiency virus (SIV)/HIV deep transmission history and current HIV evolution within the last 15-20 years. Our results confirmed that the V1V2 region of gp120 protein, particularly V1, was preferentially selected. A shorter V1 region was preferred during transmission history, while during epidemic, HIV may evolve to an expanded V1 region gradually and thus escape immune recognition. We then constructed different HIV-1 V1 mutants using different HIV-1 subtypes to elucidate the role of the V1 region in envelope function. We found that the V1 region, although highly variable, was indispensable for virus entry and infection, probably because V1 deletion mutants exhibited impaired processing of gp160 into mature gp120 and gp41. Additionally, the V1 region affected Env incorporation. These results indicated that the V1 region played a critical role in HIV transmission and infection.

The Epidemic Dynamics of Four Major Lineages of HIV-1 CRF01_AE Strains After Their Introduction into China.

The epidemic of HIV-1 CRF01_AE in China was driven by multiple lineages of HIV-1 viruses introduced in the 1990s and increasing; it is important to investigate their epidemic status in China. In this study, we download all available CRF01_AE sequences (n = 2,931) from China and their associated epidemiological information in the Los Alamos HIV database for our analysis to explore their epidemic status in China. The results showed there were 11 distinct clusters of CRF01_AE strains in China, and 4 major clusters that accounted for 80.0% (1,793/2,241) of Chinese CRF01_AE strains in total had led a real epidemic. Clusters 1 and 2 were epidemic among heterosexuals and injecting drug users in southern and southwestern China, while Clusters 3 and 4 were predominant among homosexuals in eastern and central China and northeastern China, respectively. HIV-1 CRF01_AE strains detected in heterosexuals had the most complex characteristic, underscoring its important role in the occurrence of multiple CRF01_AE lineages. Furthermore, epidemic history reconstruction analysis using the birth-death susceptible-infected-removed package revealed that the four clusters had gone through varying epidemic stages. Clusters 2 and 3 were near the peak of the local epidemic, while Clusters 1 and 4 were just in the very early stage of their epidemic. The epidemic status of CRF01_AE clusters in the future is mainly determined by the effect of prevention and control. Our study provides new insights into the understanding of the epidemic dynamics of CRF01_AE in China.

The HIV-1 accessory protein Vpr induces the degradation of the anti-HIV-1 agent APOBEC3G through a VprBP-mediated proteasomal pathway.

The host anti-HIV-1 factor APOBEC3G (A3G) plays a potential role in restricting HIV-1 replication, although this antagonist can be encountered and disarmed by the Vif protein. In this paper, we report that another HIV-1 accessory protein, viral protein R (Vpr), can interact with A3G and intervene in its antiviral behavior. The interaction of Vpr and A3G was predicted by computer-based screen and confirmed by a co-immunoprecipitation (Co-IP) approach. We found that Vpr could reduce the virion encapsidation of A3G to enhance viral replication. Subsequent experiments showed that Vpr downregulated A3G through Vpr-binding protein (VprBP)-mediated proteasomal degradation, and further confirmed that the reduction of A3G encapsidation associated with Vpr was due to Vpr's degradation-inducing activity. Our findings highlight the versatility of Vpr by unveiling the hostile relationship between Vpr and A3G. In addition, the observation that A3G is targeted to the proteasomal degradation pathway by Vpr in addition to Vif implicates the existence of crosstalk between different HIV-1-host ubiquitin ligase complex systems.