Plausibilidad genética de la infección por el virus del Zika y el síndrome de Guillain-Barré / Genetic plausibility of infection by the Zika virus syndrome Guillain - Barré Syndrome

Introducción: La infección por el virus del Zika (ZIKV) es, en la mayoría de los casos, asinto-mática o se presenta como una enfermedad leve y auto-limitada, principalmente con erupción cutánea, fiebre, artralgias y conjuntivitis. Sin embargo, en algunos pacientes puede producir efectos graves en el sistema nervioso, entre los cuales se destaca el síndrome de Guillain-Ba-rré (SGB), una polirradiculoneuropatía aguda, con características autoinmunes y, por lo ge-neral, desmielinizante. Objetivo: Realizar el primer estudio de asociación del genoma com-pleto en pacientes con infección por ZIKV y en aquellos que desarrollaron SGB post-viral.

Recent advances in the study of mechanism of APOBEC3G against virus / 药学学报

APOBEC3 is a class of cytidine deaminase, which is considered as a new member of the innate immune system, and APOBEC3G belongs to this family. The research about APOBEC3G is a new direction of innate immune defense mechanism against virus. APOBEC3G has the restrictive activity on many viral replications, which deaminates dC to dU in the viral genome and then induces extensive hypermutation. APOBEC3G can also interrupt viral replication at several phases such as reverse transcription, replication, nucleocapsid and so on by non-deamination mechanisms. However, virus can encode viral proteins to counteract the restriction activity of APOBEC3G. Elucidation of the antagonistic interaction between APOBEC3G and the virus will be contributed to development of new antiviral drugs in the future.

Association between APOBEC3G polymorphisms and susceptibility to chronic hepatitis B / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the association between rs185983011 single-nucleotide polymorphisms (SNP) of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and the susceptibility to chronic hepatitis B.</p><p><b>METHODS</b>The blood samples were collected from 186 healthy subjects and 159 patients with chronic hepatitis B. The rs185983011 SNP was detected and genotyped by sequencing with Sanger's method to analyze the relationship between rs185983011 SNP and chronic hepatitis B.</p><p><b>RESULTS</b>Only C/C and C/T genotypes of the alleles of rs185983011 SNP were found in the tested subjects, and the C/C genotype was predominant (97.7%). The distribution frequencies of rs185983011 SNP genotypes and alleles showed no significant difference between healthy subjects and patients with chronic hepatitis B (P>0.05).</p><p><b>CONCLUSION</b>The predominant genotype of rs185983011 SNP of APOBEC3G is C/C in the tested subjects, and rs185983011 SNP does not appear to associate with the susceptibility to chronic hepatitis B.</p>

Tactics used by HIV-1 to evade host innate, adaptive, and intrinsic immunities / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To review the mechanisms by which HIV evades different components of the host immune system.</p><p><b>DATA SOURCES</b>This review is based on data obtained from published articles from 1991 to 2012. To perform the PubMed literature search, the following key words were input: HIV and immune evasion.</p><p><b>STUDY SELECTION</b>Articles containing information related to HIV immune evasion were selected.</p><p><b>RESULTS</b>Although HIV is able to induce vigorous antiviral immune responses, viral replication cannot be fully controlled, and neither pre-existing infected cells nor latent HIV infection can be completely eradicated. Like many other enveloped viruses, HIV can escape recognition by the innate and adaptive immune systems. Recent findings have demonstrated that HIV can also successfully evade host restriction factors, the components of intrinsic immune system, such as APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G), TRIM5α (tripartite motif 5-α), tetherin, and SAMHD1 (SAM-domain HD-domain containing protein).</p><p><b>CONCLUSIONS</b>HIV immune evasion plays an important role in HIV pathogenesis. Fully understanding the tactics deployed by HIV to evade various components of the host immune systems will allow for the development of novel strategies aimed toward the prevention and cure of HIV/AIDS.</p>

Research methods of anti-HIV-1 inhibitors targeting at Vif-APOBEC3G axis / 中国中药杂志

The mammalian APOBEC3G protein (apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 protein G, APOBEC3G) is an important component of the cellular innate immune response to retroviral infection. APOBEC3G can extinguish HIV-1 (human immunodeficiency virus type 1) infectivity by its incorporation into virus particles and subsequent cytosine deaminase activity to block replication of HIV-1. HIV-1 Vif (viral infectivity factor) suppresses various APOBEC3 proteins through a common mechanism which induces the degradation of target proteins. Therefore, the interrelation of Vif-APOBEC3G has been extensively studied, which represents attractive targets for the development of novel inhibitors. We summarize the papers in which the detection technique and methods have been developed to assay the anti-HIV activity and its mechanism, such as western-blotting, co-immunoprecipitation, pulse-chase experiments, bioluminescence resonance energy transfer, biomolecular interaction analysis. This review is towards developing therapeutics aimed at the Vif-APOBEC3G axis.

Expression and subcellular localization of APOBEC3G in peripheral blood mononuclear cells and liver tissues of chronic HBV patients / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the expression level and intracellular localization of APOBEC3G in peripheral blood mononuclear cells (PBMCs) and liver tissues of chronic HBV patients.</p><p><b>METHODS</b>The expression level and intracellular localization of APOBEC3G in PBMCs and liver tissues were detected using the western blot and confocal laser scanning microscope (CLSM).</p><p><b>RESULTS</b>Western-blot showed that the expression level of APOBEC3G in PBMCs of healthy controls was very low. The relative expression levels of APOBEC3G in PBMC of patients with chronic hepatitis B, chronic severe hepatitis, liver cirrhosis, or liver cancer were 4.12+/-0.21, 4.07+/-0.28, 4.16+/-0.36 or 4.21+/-0.39 respectively, which were higher than that in the healthy controls. However, there was no significant difference in APOBEC3G expression among different chronic HBV patients (q = 0.931, 0.744, 1.675, 1.675, 2.606 or 0.931, respectively, all P values more than 0.05). In addition, there was no significant difference on APOBEC3G in liver tissues between chronic hepatitis B patients and hepatocellular carcinoma patients (4.40+/-0.34 vs 4.34+/-0.43, q = 0.588, P more than 0.05). CLSM indicated that the localization of APOBEC3G protein was in cytoplasm of PBMCs and hepatocytes.</p><p><b>CONCLUSION</b>APOBEC3G is upregulated in the PBMCs of chronic hepatitis B patients.</p>

Progress in the study of HIV-1 Vif and related inhibitors / 药学学报

Human immunodeficiency virus type 1 (HIV-1) viral infectivity factor (Vif), one of the accessory proteins, which is a small basic phosphoprotein, is essential for viral replication and pathogenesis. The best well-characterized function of Vif is its ability to neutralize the host cell antiviral factor, apolipoprotein B mRNA editing enzyme catalytic polypeptide like 3G (APOBEC3G), which makes the viral particles more infective. In addition, Vif can regulate the reverse transcription and the advanced stage of replication of the virus particle, as well as induce the termination of cell cycle at G2 stage and so on. The designed drug aimed directly at Vif can efficiently block the maturation and infectivity of HIV-1. In this review, the structure, function and especially the related inhibitors of Vif are reviewed.

Inhibitory effect of a HBV vector plasmid expressing A3C on HBV replication / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the inhibitory effect of a replication-defective hepatitis B virus (HBV) vector plasmid expressing A3C on HBV replication in vitro.</p><p><b>METHODS</b>The HBV vector plasmisd pCH-LJ3-A3C and pCH-LJ3-hrGFP expressing A3C and hrGFP were constructed using PCR and gene recombination technique. The two recombinant plasmids were separately cotranfected into HepG2 cells along with the wild-type HBV plasmid pCH-3093. The HBV DNA in the cell cytoplasmic lysates and in the cell culture supernatant was extracted for Southern blotting, and the nucleocapsid-associated HBV DNA were amplified by PCR, cloned and sequenced.</p><p><b>RESULTS</b>pCH-LJ3-A3C showed obvious inhibitory effect on HBV DNA in the cytoplasmic lysates and cell culture supernatant, causing a reduction of the HBV DNA by 31% and 40%, respectively. The pCH-LJ3-A3C plasmid was capable of editing the HBV DNA. Among the 50 sequenced clones, 36 clones had G-A mutations, with a total of 982 such mutations.</p><p><b>CONCLUSION</b>pCH-LJ3-A3C can inhibit the replication of HBV primarily by editing HBV DNA. The pCH-LJ3-A3C plasmid may serve as a new antiviral agent against human HBV infection.</p>

Enhanced protein production of Vif and APOBEC3G by HIV-1 Vpr / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>Goal of this study was to test the potential regulatory effects of Vpr on Vif and Vif-mediated degradation of APOBEC3G.</p><p><b>METHODS</b>The Vpr effect was first tested in a fission yeast RE007 strain that carries a single integrated copy of vpr gene in the chromosome and transformed with a vif-expressing plasmid. Similar tests were also carried out in a muristerone A vpr-inducing HEK293 mammalian cell line that were transfected with the plasmids expressing vif and/or APOBEC3G. Western Blot analyses were used to measure the corresponding protein levels under different experimental conditions.</p><p><b>RESULTS</b>Expression of HIV-1 vpr appears to enhance the protein levels of Vif both in fission yeast and mammalian cells. A similar enhancement effect of APOBEC3G by Vpr was also detected in mammalian cells. Interestingly, however, the increased Vif protein level by Vpr did not result in more APOBEC3G degradation than without Vpr, indicating a potential regulatory effect of Vpr on Vif-mediated proteolysis of APOBEC3G.</p><p><b>CONCLUSION</b>To our knowledge, this is the first report describing a potentially conserved and regulatory effect of HIV-1 Vpr on Vif and Vif-mediated protein degradation of APOBEC3G.</p>

The associations between polymorphisms of APOBEC3G and different outcomes of persistent HBV infection / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the associations between polymorphisms of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and different outcomes of HBV infection in the Chinese Han population.</p><p><b>METHODS</b>Six hundred thirty-five chronic hepatitis B patients were divided into 3 groups: 202, 217 and 216 patients were HBV cleared, chronic hepatitis B, and with liver cirrhosis, respectively. Five tagSNPs (rs8177832, rs17000736, rs17496046, rs9622924 and rs2899313) were genotyped by pyrosequencing. HBV viral loads were determined by real-time PCR method. Chi square was used for statistics.</p><p><b>RESULTS</b>The majority of rs8177832 allele was A/A and the frequencies of rs8177832 allele among these groups were not significantly different (P more than 0.05). HBV viral loads were higher in chronic hepatitis B patients with G allele than in chronic hepatitis B patients with A allele (P less than 0.05). The rs17000736 and rs9622924 alleles were found only in G/G and C/C genotypes. There were also no significant differences in the other four SNPs alleles (rs17000736, rs17496046, rs9622924 and rs2899313) in these groups (P more than 0.05).</p><p><b>CONCLUSIONS</b>rs8177832, rs17000736, rs17496046, rs17000736 and rs2899313 of the APOBEC3G gene might not be associated with HBV persistent infection in patients in this study. However, the rs8177832 polymorphism may be involved in inhibiting HBV replication.</p>

Advances in the study of molecular mechanism of APOBEC3G anti-HIV-1 / 药学学报

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 protein G (APOBEC3G) is part of the innate immune system of host cells and has cytidine deaminase activity. It specifically incorporates into the virion during HIV-1 replication. The incorporation of APOBEC3G needs its interaction with HIV-1 Gag. In the HIV-1 reverse transcription process, APOBEC3G deaminates dC to dU in the first minus strand cDNA, and then induces extensive hypermutation in the viral genome. Besides deamination, APOBEC3G also inhibits HIV-1 by some kinds of non-deamination mechanisms which need to be further elucidated. HIV-1 Vif counteracts the activity of APOBEC3G by an ubiquitin-proteasome-mediated degradation of APOBEC3G. As a broad spectrum inhibitor of viruses, APOBEC3G also inhibits various retroviruses, retrotransposons and other viruses like HBV. Upregulating the expression of APOBEC3G or blocking the Vif-mediated degradation of APOBEC3G might be novel strategies to treat HIV-1 infection in the future.

Subcellular localization of APOBEC3G by confocal laser scanning microscope (CLSM) / 病毒学报

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) cDNA was amplified from total RNA prepared from nonpermissive H9 cells by RT-PCR. APOBEC3G cDNA is 1155nt long, encoding 384 amino acids. The APOBEC3G gene was then cloned into the eukaryotic expression vector pEGFP-C3. The generated pEGFP-3G construct was then transfected into CD4+ HeLa cell to determine the expression and the subcellular localization of GFP-APOBEC3G fusion protein. Under CLSM the localization of the expressed GFP-APOBEC3G in the cytoplasm of CD4+ HeLa cells was observed.

Inhibition of hepatitis B and duck hepatitis B virus replication by APOBEC3G / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the effect of apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) mediated antiviral activity against hepatitis B virus (HBV) and duck hepatitis B virus (DHBV).</p><p><b>METHODS</b>Total RNA was extracted from peripheral blood mononuclear cells (PBMCs), RT-PCR product was cloned into the EcoR I/Hind III restriction sites of the CMV-driven expression vector fused with a hemagglutinin fusion epitope tag at its carboxyl terminal. Replication competent 1.3 fold over-length HBV was constructed with full-length HBV of ayw subtype. The mammalian hepatoma cell HepG2 was cotransfected with the replication competent 1.3 fold over-length HBV and various amounts of CMV-driven expression vector encoding APOBEC3G-HA. Levels of HBsAg and HBeAg in the media of the transfected cells were determined by ELISA, HBV DNA. RNA from intracellular core particles was examined using Northern and Southern blot analyses. Chicken hepatoma cell LMH was cotransfected with head-to-tail dimer of an EcoR I monomer of DHBV and various amounts of CMV-driven expression vector encoding APOBEC3G-HA. DHBV DNA from intracellular core particles was examined using Southern blot analysis.</p><p><b>RESULTS</b>CMV-driven expression vector encoding APOBEC3G-HA and replication competent 1.3 fold over-length HBV were constructed. There was a dose dependent decrease in the levels of intracellular core-associated viral (HBV and DHBV) DNA and extracellular production of HBsAg and HBeAg. Levels of intracellular core-associated viral RNA were also decreased, but the expression of HBcAg remained almost unchanged.</p><p><b>CONCLUSION</b>APOBEC3G suppresses HBV and DHBV replication and also suppresses HBsAg and HBeAg expression.</p>