Inhibition Of Human Immunodeficiency Virus Replication Research Articles

Genetic polymorphisms in the C19orf66 gene influenced HIV-1 infection in a Yunnan population.

Due to the deficiencies of vaccines and effective medicine, the human immunodeficiency virus (HIV) infection mechanism should be studied. The C19orf66 gene, one of the interferon-stimulated genes (ISGs), expresses broad-spectra anti-viral activity, including inhibiting HIV replication. In this study, we collect 421 HIV-1 infected patients and 448 controls to genotype three SNPs in the C19orf66 gene. Then, the association between SNPs and biochemical indices/ HIV-1 subtypes are analyzed. Genotypes CC and CT of rs12611087 show statistically lower and higher frequencies in HIV-1 infected patients than in controls, respectively. Alleles C and T of rs12611087 play protective and risk roles in Yunnan HIV population, respectively. Biochemical indices analysis shows that HIV-1 infected persons carried genotype TT of rs77076061 express significantly lower CD3+/CD45+ ratio level and higher IBIL level. The epidemic subtypes of HIV-1 patients in this study are CRF 07_BC and CRF 08_BC. Moreover, subtype CRF 08_BC tends to infect persons with genotype CC of rs12611087. The genetic polymorphisms of the C19orf66 gene are firstly studied and reported to associate with HIV-1 infection and biochemical indices of patients in Yunnan. Furthermore, subtype CRF 08_BC infection could be influenced by genotypes of SNP in the C19orf66 gene.

The Impact of CRISPR and Cas9 on AIDS

AIDS is a chronic infectious disease caused by the human immunodeficiency virus (HIV), and the current treatment for the disease is a combination of highly effective antiretroviral therapy, consisting of a combination of at least three of these drugs to combat HIV infection. However, this therapy only inhibits HIV replication, but does not completely eliminate the virus. Once antiretroviral treatment is interrupted, the patient's disease is prone to relapse. Therefore we need gene editing, which is the process of modifying, adding, deleting and replacing information in the body's DNA in order to modify diseases caused by genetic mutations, which can only be controlled by drugs. It is hoped that in the near future, gene editing technology will revolutionise the treatment of cancer and genetic diseases, thanks to the work of scientists.

Introduction of Mutant APOBEC3G Into CD4+ T-Cells to Resist HIV-1

Introduction: Human immunodeficiency virus 1 (HIV-1) is a potentially lethal retrovirus with high genetic diversity and replication ability. HIV-1 mainly targets human CD4+ T-cells, causing a rapid decline in CD4+ T-cell count after infection. Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3G (APOBEC3G or A3G) is a human anti-viral enzyme that blocks early stages of HIV-1 replication by deaminating the cytosine residues to uracil in the viral minus-strand DNA during reverse transcription. Nevertheless, HIV-1 overcomes A3G anti-viral activity by employing Vif accessory protein to degrade A3G. Due to a proline/aspartate point mutation in residue 129 (P129D), an artificial A3G mutant, also known as A3G-P129D, was found to be resistant against diverse Vif variants, including HIV-1 Vif, thereby shedding light on a potential A3G-mediated gene therapy for HIV-1. Methods: We propose that, using CRISPR-Cas9 tools, the P129D mutation will be introduced into A3G expressed by human hematopoietic stem cells. Engineered stem cells will be transplanted into Non-Obese Diabetic Severe Combined Immunodeficient Gamma (NSG) mice, which will later be infected with HIV-1. Following infection, flow cytometry will be used to compare the CD4+ T-cell count in mice that express A3G-P129D versus control mice transplanted with unmodified human CD4+ T-cells. Results: We expect a notably higher CD4+ T-cell count in mice carrying the P129D mutation than in the control group, which would be attributed to the efficient inhibition of HIV-1 replication by the mutant A3G. Discussion: Transforming human A3G to A3G-P129D will prevent Vif-mediated degradation of A3G, allowing A3G to efficiently target HIV-1. Thus, this treatment would ultimately block HIV-1 replication and prevent CD4+ T-cell depletion. Conclusion: Overall, our novel gene therapy approach could open the door to a potential one-time treatment for HIV-1 infected patients.

Research Progress on the Relationship between the NLRP3 Inflammasome and Immune Reconstitution in HIV-Infected Patients Receiving Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection is characterized not only by severe immunodeficiency but also by persistent inflammation and immune activation. These characteristics persist in people living with HIV (PLHIV) receiving effective antiretroviral therapy (ART) and are associated with morbidity and mortality in nonacquired immunodeficiency syndrome (AIDS) events. ART can inhibit HIV replication and promote immune reconstitution, which is currently the most effective way to control AIDS. However, despite effective long-term ART and overall suppression of plasma HIV RNA level, PLHIV still shows chronic low-level inflammation. The exact mechanisms that trigger chronic inflammation are unknown. Activation of the inflammasome is essential for the host response to pathogens, and some recent studies have confirmed the role of the inflammasome in the pathogenesis of inflammatory diseases. The NLRP3 inflammasome has been widely studied, which is a pyrin domain-containing protein 3 belonging to the family of nucleotide-binding and oligomerization domain-like receptors (NLRs). Recent studies suggest that inflammasome-mediated pyroptosis is associated with CD4+ T cell loss in the absence of persistent infectious HIV replication. This article reviews the mechanism of the NLRP3 inflammasome and its correlation with immune reconstitution in PLHIV treated with ART.

Negative Regulation and Protective Function of Natural Killer Cells in HIV Infection: Two Sides of a Coin.

Natural killer (NK) cells play an important immunologic role, targeting tumors and virus-infected cells; however, NK cells do not impede the progression of human immunodeficiency virus (HIV) infection. In HIV infection, NK cells exhibit impaired functions and negatively regulate other immune cell responses, although NK cells can kill HIV-infected cells and thereby suppress HIV replication. Considerable recent research has emerged regarding NK cells in the areas of immune checkpoints, negative regulation, antibody-dependent cell-mediated cytotoxicity and HIV reservoirs during HIV infection; however, no overall summary of these factors is available. This review focuses on several important aspects of NK cells in relation to HIV infection, including changes in NK cell count, subpopulations, and immune checkpoints, as well as abnormalities in NK cell functions and NK cell negative regulation. The protective function of NK cells in inhibiting HIV replication to reduce the viral reservoir and approaches for enhancing NK cell functions are also summarized.

Human immunodeficiency virus: The potential of medicinal plants as antiretroviral therapy.

Human immunodeficiency virus (HIV) infection is fast becoming widespread in the world with 37.7 million people living with HIV in 2020. Antiretroviral therapy involving chemical drugs has declined acquired immunodeficiency syndrome (AIDS)-related mortality and improved the life quality of AIDS/HIV sufferers. However, the emergence of drug resistance and side effects are the main obstacles for the long-term use of these chemicals as antiretroviral therapy. Recently, a lot of emphasis is being put on finding naturally occurring drug candidates that show activity against HIV and can be potentially used as antiretroviral therapy. In this study, different medicinal plants, Pistacia khinjuk, Teucrium stocksianum, Uncaria tomentosa, Pistacia integerrima, Trigonella gharuensis, and Artocarpus lakoocha, were explored for their anti-HIV potential. Syncytium and p24 assays were performed to determine antiviral activity, while the MTT assay was used to determine cytotoxicity. Results showed that extracts from all six plants inhibited HIV replication in vitro. Also, extracts from Pistaciakhinjuk, Teucrium stocksianum, Uncaria tomentosa, and Pistacia integerrima showed low cytotoxicity with a 50% cytotoxicity concentration value of >200 μM. Results of this study indicate that there is potential in these natural extracts to become candidate drugs to be used as complementary and alternative medicine for HIV infection.

Antimicrobial Peptide, LL-37, And Its Potential As An Anti-HIV Agent.

Human immunodeficiency virus (HIV) continues to have a profound global health impact. New infections continue at a high rate despite the development of prophylactic therapies, prompting the need for development of novel preventative approaches. Antimicrobial peptides (AMPs), such as LL-37, display broad microbicidal properties and have potential as anti-HIV agents. LL-37 has been studied for its anti-HIV activity and the limited data available suggest it can inhibit HIV infection in primary T cells as well as exert inhibitory effects on key HIV enzymes. Its immunomodulatory properties may both enhance and inhibit HIV replication. In addition, LL-37 has both 1) the ability to kill other sexually-transmitted pathogens and 2) spermicidal activity; thus, it is a good candidate for multipurpose prevention technology. Further investigation of its anti-HIV activity is warranted.

Development of 7SK snRNA Mimics That Inhibit HIV Transcription.

The 332-nucleotide small nuclear RNA (snRNA) 7SK is a highly conserved non-coding RNA that regulates transcriptional elongation. By binding with positive transcriptional elongation factor b (P-TEFb) via HEXIM1, 7SK snRNA decreases the kinase activity of P-TEFb and inhibits transcriptional elongation. Additionally, it is reported that 7SK inhibition results in the stimulation of human immunodeficiency virus (HIV)-specific transcription. These reports suggest that 7SK is a naturally occurring functional molecule as negative regulator of P-TEFb and HIV transcription. In this study, we developed functional oligonucleotides that mimic the function of 7SK (7SK mimics) as novel inhibitors of HIV replication. We defined the essential region of 7SK regarding its suppressive effects on transcriptional downregulation using an antisense strategy. Based on the results, we designed 7SK mimics containing the defined region. The inhibitory effects of 7SK mimics on HIV-1 long terminal repeat promoter specific transcription was drastic compared with those of the control mimic molecule. Notably, these effects were found to be more enhanced by co-transfection with Tat-expressing plasmids. From these results, it is indicated that 7SK mimics may have great therapeutic potential for HIV/AIDS treatment.

Research progress on influencing factors of antiretroviral therapy withdrawal in HIV/AIDS patients

AIDS is a highly harmful infectious disease caused by human immunodeficiency virus (HIV), which requires HIV/AIDS patients to take medication on time and at the appropriate amount every day to effectively inhibit HIV replication in vivo. China has implemented antiretroviral therapy (ART) and expanded treatment strategy, including all eligible HIV-infected people into the treatment scope of treatment. More and more HIV-infected patients receive ART. At the same time, the number of HIV/AIDS patients who withdraw from ART (drug withdrawal and loss of follow-up) is also increasing year by year. In the long-term medication process of HIV/AIDS patients, various reasons such as adverse drug reactions, busy work, CD4, low selfmanagement ability of patients, economic conditions and other reasons lead to poor compliance of patients and high incidence of withdrawal. In China, ART treatment coverage of HIV/AIDS patients is required to be over 90%, and withdrawal has become the biggest threat to the coverage of ART treatment. In this paper, the influencing factors related to ART withdrawal of HIV/ AIDS patients were summarized to comprehensively understand the reasons for the possible withdrawal of ART therapy for HIV/ AIDS patients, and to provide measures to reduce the withdrawal and loss of follow-up of ART therapy for HIV/AIDS patients. 摘要 : 艾滋病是由人类免疫缺陷病毒(HIV)引起的一种危害性极大的传染病, 需要 HIV/AIDS 患者每日按时按量服 药才能有效抑制体内 HIV 复制。中国实施抗逆转录病毒疗法(ART)和扩大治疗策略将所有符合条件的 HIV 感染者纳人 治疗范围, 越来越多的 HIV 感染者接受ART,同时退出 (停药和失访)ART的 HIV/AIDS 患者人数也在逐年累加。在 HIV/AIDS 患者长期的服药过程中, 药物不良反应、工作繁忙、CD4、患者自我管理能力低、经济条件等各种原因, 导致患 者出现依从性不良 , 患者退出的发生率髙。中国遏制与防治艾滋病要求 HIV/AIDS 患者 ART 治疗覆盖率是90%以上, 退出已经成为影响ART治疗覆盖率的最大威胁。本文就 HIV/AIDS 患者 ART 退出相关影响因素进行综述, 全面了解 HIV/AIDS 患者ART治疗可能退出的原因以及提供减少 HIV/AIDS 患者ART治疗停药和失访相关措施。

Fingolimod inhibits multiple stages of the HIV-1 life cycle.

Antiretroviral drugs that target various stages of the Human Immunodeficiency Virus (HIV) life cycle have been effective in curbing the AIDS epidemic. However, drug resistance, off-target effects of antiretroviral therapy (ART), and varying efficacy in prevention underscore the need to develop novel and alternative therapeutics. In this study, we investigated whether targeting the signaling molecule Sphingosine-1-phosphate (S1P) would inhibit HIV-1 infection and generation of the latent reservoir in primary CD4 T cells. We show that FTY720 (Fingolimod), an FDA-approved functional antagonist of S1P receptors, blocks cell-free and cell-to-cell transmission of HIV and consequently reduces detectable latent virus. Mechanistically, FTY720 impacts the HIV-1 life cycle at two levels. Firstly, FTY720 reduces the surface density of CD4, thereby inhibiting viral binding and fusion. Secondly, FTY720 decreases the phosphorylation of the innate HIV restriction factor SAMHD1 which is associated with reduced levels of total and integrated HIV, while reducing the expression of Cyclin D3. In conclusion, targeting the S1P pathway with FTY720 could be a novel strategy to inhibit HIV replication and reduce the seeding of the latent reservoir.

Inhibition of HIV replication through siRNA carried by CXCR4-targeted chimeric nanobody.

Small interfering RNA (siRNA) application in therapy still faces a major challenge with the lack of an efficient and specific delivery system. Current vehicles are often responsible for poor efficacy, safety concerns, and burden costs of siRNA-based therapeutics. Here, we describe a novel strategy for targeted delivery of siRNA molecules to inhibit human immunodeficiency virus (HIV) infection. Specific membrane translocation of siRNA inhibitor was addressed by an engineered nanobody targeting the HIV co-receptor CXCR4 (NbCXCR4) in fusion with a single-chain variable fragment (4M5.3) that carried the FITC-conjugated siRNA. 4M5.3-NbCXCR4 conjugate (4M5.3X4) efficiently targeted CXCR4+ T lymphocytes, specifically translocating siRNA by receptor-mediated endocytosis. Targeted delivery of siRNA directed to the mRNA of HIV transactivator tat silenced Tat-driven viral transcription and inhibited the replication of distinct virus clades. In summary, we have shown that the engineered nanobody chimera developed in this study constitutes an efficient and specific delivery method of siRNAs through CXCR4 receptor.

Dual activity of niclosamide to suppress replication of integrated HIV-1 and Mycobacterium tuberculosis (Beijing)

The human immunodeficiency virus (HIV) pandemic is driving the re-emergence of tuberculosis (TB) as a global health threat, both by increasing the susceptibility of HIV-infected people to infection with Mycobacterium tuberculosis (Mtb), and increasing the rate of emergence of drug-resistant Mtb. There are several other clinical challenges for treatment of co-infected patients including: expense, pill burden, toxicity, and malabsorption that further necessitate the search for new drugs that may be effective against both pathogens simultaneously. The anti-helminthic niclosamide has been shown to have activity against a laboratory strain of Mtb in liquid culture while bacteriostatic activity against non-replicating M. abscessus was also recently described. Here we extend these findings to further demonstrate that niclosamide inhibits mycobacterial growth in infected human macrophages and mediates potent bacteriostatic activity against the virulent Mtb Beijing strain. Importantly, we provide the first evidence that niclosamide inhibits HIV replication in human macrophages and Jurkat T cells through post-integration effects on pro-virus transcription. The dual antiviral and anti-mycobacterial activity was further observed in an in vitro model of HIV and Mtb co-infection using human primary monocyte-derived macrophages. These results support further investigation of niclosamide and derivatives as anti-retroviral/anti-mycobacterial agents that may reduce clinical challenges associated with multi-drug regimens and drug resistance.

Molecular dissection of an inhibitor targeting the HIV integrase dependent preintegration complex nuclear import.

Human immunodeficiency virus (HIV) continues to be a major contributor to morbidity and mortality worldwide, particularly in developing nations where high cost and logistical issues severely limit the use of current HIV therapeutics. This, combined HIV's high propensity to develop resistance, means that new antiviral agents against novel targets are still urgently required. We previously identified novel anti‐HIV agents directed against the nuclear import of the HIV integrase (IN) protein, which plays critical roles in the HIV lifecycle inside the cell nucleus, as well as in transporting the HIV preintegration complex (PIC) into the nucleus. Here we investigate the structure activity relationship of a series of these compounds for the first time, including a newly identified anti‐IN compound, budesonide, showing that the extent of binding to the IN core domain correlates directly with the ability of the compound to inhibit IN nuclear transport in a permeabilised cell system. Importantly, compounds that inhibited the nuclear transport of IN were found to significantly decrease HIV viral replication, even in a dividing cell system. Significantly, budesonide or its analogue flunisolide, were able to effect a significant reduction in the presence of specific nuclear forms of the HIV DNA (2‐LTR circles), suggesting that the inhibitors work though blocking IN, and potentially PIC, nuclear import. The work presented here represents a platform for further development of these specific inhibitors of HIV replication with therapeutic and prophylactic potential.

Optimization of Polycistronic Anti-CCR5 Artificial microRNA Leads to Improved Accuracy of Its Lentiviral Vector Transfer and More Potent Inhibition of HIV-1 in CD4⁺ T-Cells.

C-C chemokine receptor type 5 (CCR5) is utilized by human immunodeficiency virus (HIV) as a co-receptor for cell entry. Suppression of the CCR5 gene by artificial microRNAs (amiRNAs) could confer cell resistance. In previous work, we created a lentivector that encoded the polycistron of two identical amiRNAs that could effectively suppress CCR5. However, tandem repeats in lentiviral vectors led to deletions of the repeated sequences during reverse transcription of the vector RNA. To solve this problem, we have created a new amiRNA against CCR5, mic1002, which has a different microRNA scaffold and targets a different sequence. Replacing one of the two identical tandem amiRNAs in the polycistron with the mic1002 amiRNA increased the accuracy of its lentiviral vector transfer while retaining its ability to effectively suppress CCR5. A lentiviral vector containing two heterogenic amiRNAs significantly inhibited HIV replication in a vector-transduced human CD4+ lymphocyte culture.

Development of antibody-modified chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier as a strategy for inhibiting HIV replication in astrocytes.

RNA interference (RNAi)-mediated gene silencing offers a novel treatment and prevention strategy for human immunodeficiency virus (HIV) infection. HIV was found to infect and replicate in human brain cells and can cause neuroinfections and neurological deterioration. We designed dual-antibody-modified chitosan/small interfering RNA (siRNA) nanoparticles to deliver siRNA across the blood-brain barrier (BBB) targeting HIV-infected brain astrocytes as a strategy for inhibiting HIV replication. We hypothesized that transferrin antibody and bradykinin B2 antibody could specifically bind to the transferrin receptor (TfR) and bradykinin B2 receptor (B2R), respectively, and deliver siRNA across the BBB into astrocytes as potential targeting ligands. In this study, chitosan nanoparticles (CS-NPs) were prepared by a complex coacervation method in the presence of siRNA, and antibody was chemically conjugated to the nanoparticles. The antibody-modified chitosan nanoparticles (Ab-CS-NPs) were spherical in shape, with an average particle size of 235.7±10.2nm and a zeta potential of 22.88±1.78mV. The therapeutic potential of the nanoparticles was evaluated based on their cellular uptake and gene silencing efficiency. Cellular accumulation and gene silencing efficiency of Ab-CS-NPs in astrocytes were significantly improved compared to non-modified CS-NPs and single-antibody-modified CS-NPs. These results suggest that the combination of anti-Tf antibody and anti-B2 antibody significantly increased the knockdown effect of siRNA-loaded nanoparticles. Thus, antibody-mediated dual-targeting nanoparticles are an efficient and promising delivery strategy for inhibiting HIV replication in astrocytes. Graphical abstract Graphic representation of dual-antibody-conjugated chitosan nanoparticles for the targeted delivery of siRNA across the blood-brain barrier (BBB) for inhibiting HIV replication in astrocytes. a Nanoparticle delivery to the BBB and penetration. b TfR-mediated transcytosis of nanoparticles across the epithelial cells. c B2R-mediated endocytosis of nanoparticles in astrocytes. d The molecular interactions between HIV-1 Tat protein and Cyclin T1 and Tip110 cellular proteins. e A schematic representation of chitosan nanoparticles with its components. RNAPII RNA polymerase II, TAR transactivation response RNA element, LTR long terminal repeat, Ab antibody, CS chitosan, TPP tripolyphosphate.

Study of miR-29a-5p Expression in HIV Positive and HIV/HCV Co-Infected Patients in Sanandaj-Iran

Background: Co-infection of human immunodeficiency virus (HIV) with hepatitis virus accelerates liver injury. Recently, there has been paid more attention to micro RNAs (miRs) as new tools for determination of liver injury. Previous studies revealed that miR-29 inhibits HIV replication. It has been also shown that miR-29 decreases in hepatocytes of hepatitis C virus (HCV) infected patients. The present study aimed to determine the miR-29a-5p expression as a possible diagnostic marker in HIV- and HIV-HCV co-infected patients. Methods: In this cross-sectional study, blood samples were collected from 40 healthy, 44 HIV-positive, and 121 HIV/HCV co-infected subjects. Blood CD4+ (cluster of differentiation 4) cell counts were recorded and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities, miR-29a-5p expression, fibrosis-4 (FIB-4), and AST to platelet ratio index (APRI) index were determined. Data were analyzed by SPSS version 16 and p value less than 0.05 was considered statistically significant. Results: Serum ALT and AST activities and FIB-4 and APRI were significantly higher in HIV-HCV-co-infection group than the control group (P< 0.05); however, miR-29a-5p was down-regulated in patients compared to controls. CD4+ cell counts markedly decreased in all patients and showed a significant direct correlation with miR-29a-5p (rs = 0.225, P < 0.045). The inverse significant correlation of FIB4 and APRI with miR-29a-5p expression was also seen (rs = -0.691, P = 0.005 and rs = -0.712, p<0.001, respectively). Conclusions: miR-29a-5p was significantly down-regulated in HIV- and HIV/HCV-co-infected patients and showed a correlation with liver injury. Down-regulation of miR-29a-5p was directly associated with CD4+ cell counts and reversely correlated with FIB-4 and APRI index. Therefore, the determination of miR-29a-5p may be useful, among other markers, for diagnosis of these diseases.

Lipopolysaccharide suppresses human immunodeficiency virus 1 reverse transcription in macrophages.

HIV-1-infected macrophages are long-lived and act as human immunodeficiency virus 1 (HIV-1) virus reservoirs. Lipopolysaccharide (LPS) has been demonstrated to suppress HIV-1 replication in macrophages, but the mechanism is not clear. Previous research suggested that downregulation of CD4 and CCR5 as well as blockage of the interaction of HIV-1 with cells are major causes of inhibition of HIV-1 replication in macrophages by LPS. In order to study whether LPS blocks the post-entry event of HIV-1 replication, we developed a macrophage HIV-1 infection model by using VSV-G pseudotyped HIV-1-luciferase virus to infect THP-1 differentiated macrophage-like cells. We found that LPS can suppress HIV-1 replication at post-entry steps. Further study suggested that HIV-1 reverse transcription was blocked by LPS, but addition of exogenous deoxyribonucleosides led to only partial recovery of HIV-1 replication. However, the inhibition of pro-inflammatory pathway completely rescued HIV-1 replication. Thus, our study shows that LPS can suppress the events of HIV-1 replication post-entry, including reverse transcription, and this restriction is mediated by more than one mechanism.

HIV infection.

More than 75 million people worldwide have been infected with human immunodeficiency virus (HIV), and there are now approximately 37 million individuals living with the infection. Untreated HIV replication causes progressive CD4(+) T cell loss and a wide range of immunological abnormalities, leading to an increased risk of infectious and oncological complications. HIV infection also contributes to cardiovascular disease, bone disease, renal and hepatic dysfunction and several other common morbidities. Antiretroviral drugs are highly effective at inhibiting HIV replication, and for individuals who can access and adhere to these drugs, combination antiretroviral therapy leads to durable (and probably lifelong) suppression of viral replication. Viral suppression enables immune recovery and the near elimination of the risk for developing acquired immune deficiency syndrome (AIDS). Despite effective treatment, HIV-infected individuals have a higher than expected risk of heart, bone, liver, kidney and neurological disease. When used optimally by an infected (or by an uninfected) person, antiretroviral drugs can virtually eliminate the risk of HIV transmission. Despite major advances in prevention sciences, HIV transmission remains common in many vulnerable populations, including men who have sex with men, injection drug users and sex workers. Owing to a lack of widespread HIV testing and the costs and toxicities associated with antiretroviral drugs, the majority of the infected population is not on effective antiretroviral therapy. To reverse the pandemic, improved prevention, treatment and implementation approaches are necessary.

Roles of microRNAs and long-noncoding RNAs in human immunodeficiency virus replication.

MicroRNAs (miRNAs) and long-noncoding RNAs (lncRNAs) are involved in many biological processes, including viral replication. In this review, the role of miRNAs and lncRNAs in human immunodeficiency virus (HIV) replication will be discussed. The review focuses on miRNAs that target cellular proteins involved in HIV replication-proteins that mediate steps in the viral life cycle, as well as proteins of the innate immune system that inhibit HIV replication. Given the large number of miRNAs encoded in the human genome, as well as the large number of cellular proteins involved in HIV replication, the number of miRNAs identified to date that affect viral replication are certainly only the 'tip of the iceberg'. The review also discusses two lncRNAs that are involved in HIV gene regulation-7SK RNA and NEAT1 RNA. 7SK RNA is involved in HIV Tat protein stimulation of RNA polymerase II elongation of the integrated provirus, while NEAT1 RNA is involved in HIV Rev protein export of incompletely spliced viral transcripts.

Baculovirus Infection of Human Monocyte-Derived Dendritic Cells Restricts HIV-1 Replication.

Acquired immune deficiency syndrome (AIDS) is mainly caused by infection with human immunodeficiency virus-1 (HIV-1) and still poses a global threat for which we lack a protective or therapeutic vaccine. Dendritic cells (DCs) play a major role in the onset of HIV infection, providing one of the primary sites of HIV replication, and also act as viral reservoirs in vivo. Previous studies have shown that baculovirus (BV) induces strong host immune responses against infections and malignancies. In this study, we infected human monocyte-derived DCs with recombinant BV (AcCAG-gag) and showed that AcCAG-gag-infected human DCs underwent maturation and produced interferon alpha and other proinflammatory cytokines accompanied by increases in the mRNA and protein expression levels of APOBEC3 (A3A, A3F, and A3G), proteins associated with the inhibition of HIV-1 replication. Surprisingly, HIV-1 inhibition is also observed in human DCs infected with a wild-type BV, as determined by the production of inflammatory cytokines, the expression of A3, and a reduction in the p24 level. Our findings outline the mechanism underlying the inhibition of HIV-1 in BV-infected human DCs and pave the way for the use of BV as an effective tool for immunotherapy against HIV-1.