Nicotinamide adenine dinucleotide (NAD) is a critical component of the cellular metabolism and also serves as an alternative 5' cap on various RNAs. However, the function of the NAD RNA cap is still under investigation. We studied NAD capping of RNAs in HIV-1-infected cells because HIV-1 is responsible for the depletion of the NAD/NADH cellular pool and causing intracellular pellagra. By applying the NAD captureSeq protocol to HIV-1-infected and uninfected cells, we revealed that four snRNAs (e.g., U1) and four snoRNAs lost their NAD cap when infected with HIV-1. Here, we provide evidence that the presence of the NAD cap decreases the stability of the U1/HIV-1 pre-mRNA duplex. Additionally, we demonstrate that reducing the quantity of NAD-capped RNA by overexpressing the NAD RNA decapping enzyme DXO results in an increase in HIV-1 infectivity. This suggests that NAD capping is unfavorable for HIV-1 and plays a role in its infectivity.

• MeSH
• HIV infekce * virologie   metabolismus   MeSH
• HIV-1 * MeSH
• lidé MeSH
• malá jadérková RNA * metabolismus   genetika   MeSH
• NAD * metabolismus   MeSH
• RNA čepičky metabolismus   MeSH
• RNA malá jaderná * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• císařský řez normy   MeSH
• gravidita MeSH
• HIV infekce * diagnóza   farmakoterapie   krev   virologie   MeSH
• infekční komplikace v těhotenství farmakoterapie   MeSH
• lidé MeSH
• vertikální přenos infekce MeSH
• vysoce aktivní antiretrovirová terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: There is currently no evidence suggesting that COVID-19 takes a different course in HIV-positive patients on antiretroviral treatment compared to the general population. However, little is known about the relation between specific HIV-related factors and the severity of the COVID-19 disease. METHODS: We performed a retrospective analysis of cases collected through an on-line survey distributed by the Euroguidelines in Central and Eastern Europe Network Group. In statistical analyses characteristics of HIV-positive patients, asymptomatic/moderate and moderate/severe course were compared. RESULTS: In total 34 HIV-positive patients diagnosed with COVID-19 were reported by 12 countries (Estonia, Czech Republic, Lithuania, Albania, Belarus, Romania, Serbia, Bosnia and Herzegovina, Poland, Russia, Hungary, Bulgaria). Asymptomatic courses of COVID-19 were reported in four (12%) cases, 11 (32%) patients presented with mild disease not requiring hospitalization, moderate disease with respiratory and/or systemic symptoms was observed in 14 (41%) cases, and severe disease with respiratory failure was found in five (15%) patients. The HIV-related characteristics of patients with an asymptomatic/mild course of COVID-19 were comparable to those with a moderate/severe course of COVID-19, except for the use of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in cART regimen (0.0% vs. 31.6% respectively, p = 0.0239). CONCLUSIONS: In our analyses HIV viral suppression and immunological status were not associated with the course of COVID-19 disease. On the contrary the cART regimen could contribute to severity of SARS-CoV-2 infection. Large and prospective studies are necessary to further investigate this relationship.

• MeSH
• antiretrovirové látky terapeutické užití   MeSH
• COVID-19 komplikace   virologie   MeSH
• dospělí MeSH
• farmakoterapie COVID-19 MeSH
• HIV infekce komplikace   farmakoterapie   virologie   MeSH
• inhibitory proteas terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• retrospektivní studie MeSH
• SARS-CoV-2 * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• východní Evropa MeSH

During the last two decades, progresses in bioimaging and the development of various strategies to fluorescently label the viral components opened a wide range of possibilities to visualize the early phase of Human Immunodeficiency Virus 1 (HIV-1) life cycle directly in infected cells. After fusion of the viral envelope with the cell membrane, the viral core is released into the cytoplasm and the viral RNA (vRNA) is retro-transcribed into DNA by the reverse transcriptase. During this process, the RNA-based viral complex transforms into a pre-integration complex (PIC), composed of the viral genomic DNA (vDNA) coated with viral and host cellular proteins. The protective capsid shell disassembles during a process called uncoating. The viral genome is transported into the cell nucleus and integrates into the host cell chromatin. Unlike biochemical approaches that provide global data about the whole population of viral particles, imaging techniques enable following individual viruses on a single particle level. In this context, quantitative microscopy has brought original data shedding light on the dynamics of the viral entry into the host cell, the cytoplasmic transport, the nuclear import, and the selection of the integration site. In parallel, multi-color imaging studies have elucidated the mechanism of action of host cell factors implicated in HIV-1 viral cycle progression. In this review, we describe the labeling strategies used for HIV-1 fluorescence imaging and report on the main advancements that imaging studies have brought in the understanding of the infection mechanisms from the viral entry into the host cell until the provirus integration step.

• MeSH
• buněčné jádro virologie   MeSH
• fluorescenční mikroskopie MeSH
• HIV infekce virologie   MeSH
• HIV-1 chemie   genetika   fyziologie   MeSH
• integrace viru MeSH
• internalizace viru * MeSH
• lidé MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

• MeSH
• HIV infekce * diagnóza   farmakoterapie   virologie   MeSH
• inhibitory HIV-integrasy farmakologie   terapeutické užití   MeSH
• inhibitory HIV-proteasy farmakologie   imunologie   terapeutické užití   MeSH
• inhibitory syntézy nukleových kyselin farmakologie   terapeutické užití   MeSH
• inhibitory virových proteáz farmakologie   imunologie   terapeutické užití   MeSH
• léky s prodlouženým účinkem MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• RNA virová účinky léků   MeSH
• vakcíny proti AIDS MeSH
• virová nálož účinky léků   MeSH
• vysoce aktivní antiretrovirová terapie metody   MeSH
• Check Tag
• lidé MeSH

BACKGROUND: Men in sub-Saharan Africa are less likely than women to get tested for HIV, less likely to present for treatment, less likely to be maintained in treatment, more likely to have detectable viral load, more likely to transmit HIV with unprotected intercourse, and more likely to progress to AIDS and die sooner from HIV. The ultimate objective of this research is to provide evidence-based strategies to improve HIV testing and treatment of HIV-infected men. METHODS: This study is being conducted in the Greater Edendale Area and Vulindlela region in KwaZulu-Natal, South Africa. It is a two-stage design of a cluster-randomized trial and an individual randomized trial to test how structural and individual-level interventions address the demand-side factors that affect HIV testing and treatment for hard-to reach, high-risk men. It combines male-focused mobilization, community-based mobile HIV testing services, and a small incentive to determine if the strategies singly and in combination can result in more men diagnosed with HIV, and more men linked to and maintained in care with undetectable viral load. DISCUSSION: A priority for sub-Sahara Africa is developing and evaluating novel and cost-effective strategies for identifying hard-to-reach groups such as men, linking them to HIV testing and care services, and maintaining them in care to the point of viral suppression. We propose a combination prevention intervention that addresses men's individual, interpersonal, and structural barriers to testing and care. This includes male-led mobilization to encourage uptake of testing and treatment, male-focused testing venues, male-only counselors, developing counseling models that are flexible and responsive to men, and strategies for adhering to clinic visits without missing work and navigating the healthcare system. By thoughtfully combining male-focused mobilization, and testing and addressing some of the barriers to male engagement with health facilities, this study hopes to add to the growing evidence base about how to reach, test, link, and maintain a hard-to-reach group such as men in HIV treatment and care services. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03794245. Registered on 4 January 2019.

• MeSH
• adherence a compliance při léčbě * MeSH
• ELISA MeSH
• HIV infekce diagnóza   farmakoterapie   epidemiologie   virologie   MeSH
• HIV imunologie   MeSH
• lidé MeSH
• následné studie MeSH
• plošný screening MeSH
• poradenství MeSH
• poskytování zdravotní péče metody   MeSH
• prevalence MeSH
• sexuální faktory MeSH
• virová nálož MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Jihoafrická republika MeSH

P-glycoprotein (ABCB1), an ATP-binding-cassette efflux transporter, limits intestinal absorption of its substrates and is a common site of drug-drug interactions (DDIs). ABCB1 has been suggested to interact with many antivirals used to treat HIV and/or chronic hepatitis C virus (HCV) infections. Using bidirectional transport experiments in Caco-2 cells and a recently established ex vivo model of accumulation in precision-cut intestinal slices (PCIS) prepared from rat ileum or human jejunum, we evaluated the potential of anti-HIV and anti-HCV antivirals to inhibit intestinal ABCB1. Lopinavir, ritonavir, saquinavir, atazanavir, maraviroc, ledipasvir, and daclatasvir inhibited the efflux of a model ABCB1 substrate, rhodamine 123 (RHD123), in Caco-2 cells and rat-derived PCIS. Lopinavir, ritonavir, saquinavir, and atazanavir also significantly inhibited RHD123 efflux in human-derived PCIS, while possible interindividual variability was observed in the inhibition of intestinal ABCB1 by maraviroc, ledipasvir, and daclatasvir. Abacavir, zidovudine, tenofovir disoproxil fumarate, etravirine, and rilpivirine did not inhibit intestinal ABCB1. In conclusion, using recently established ex vivo methods for measuring drug accumulation in rat- and human-derived PCIS, we have demonstrated that some antivirals have a high potential for DDIs on intestinal ABCB1. Our data help clarify the molecular mechanisms responsible for reported increases in the bioavailability of ABCB1 substrates, including antivirals and drugs prescribed to treat comorbidity. These results could help guide the selection of combination pharmacotherapies and/or suitable dosing schemes for patients infected with HIV and/or HCV.

• MeSH
• antivirové látky farmakologie   MeSH
• atazanavir sulfát farmakologie   MeSH
• benzimidazoly farmakologie   MeSH
• Caco-2 buňky účinky léků   metabolismus   MeSH
• fluoreny farmakologie   MeSH
• hepatitida C komplikace   farmakoterapie   virologie   MeSH
• HIV infekce komplikace   farmakoterapie   virologie   MeSH
• imidazoly farmakologie   MeSH
• krysa rodu rattus MeSH
• látky proti HIV farmakologie   MeSH
• lékové interakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• Lopinavir farmakologie   MeSH
• maravirok farmakologie   MeSH
• P-glykoprotein antagonisté a inhibitory   metabolismus   MeSH
• potkani Wistar MeSH
• ritonavir farmakologie   MeSH
• saquinavir farmakologie   MeSH
• senioři MeSH
• střeva účinky léků   MeSH
• zidovudin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The HIV-1 protein Rev is essential for virus replication and ensures the expression of partially spliced and unspliced transcripts. We identified a ULM (UHM ligand motif) motif in the Arginine-Rich Motif (ARM) of the Rev protein. ULMs (UHM ligand motif) mediate protein interactions during spliceosome assembly by binding to UHM (U2AF homology motifs) domains. Using NMR, biophysical methods and crystallography we show that the Rev ULM binds to the UHMs of U2AF65 and SPF45. The highly conserved Trp45 in the Rev ULM is crucial for UHM binding in vitro, for Rev co-precipitation with U2AF65 in human cells and for proper processing of HIV transcripts. Thus, Rev-ULM interactions with UHM splicing factors contribute to the regulation of HIV-1 transcript processing, also at the splicing level. The Rev ULM is an example of viral mimicry of host short linear motifs that enables the virus to interfere with the host molecular machinery.

• MeSH
• alternativní sestřih genetika   MeSH
• aminokyselinové motivy genetika   MeSH
• arginin genetika   MeSH
• genové produkty rev - virus lidské imunodeficience genetika   MeSH
• HIV infekce genetika   virologie   MeSH
• HIV-1 genetika   patogenita   MeSH
• interakce hostitele a patogenu genetika   MeSH
• lidé MeSH
• regulace exprese virových genů genetika   MeSH
• replikace viru genetika   MeSH
• sestřihové faktory genetika   MeSH
• sestřihový faktor U2AF genetika   MeSH
• spliceozomy genetika   MeSH
• vazba proteinů genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The development of an effective vaccine preventing HIV-1 infection is hindered by the enormous antigenic variability and unique biochemical and immunological properties of HIV-1 Env glycoprotein, the most promising target for HIV-1 neutralizing antibody. Functional studies of rare elite neutralizers led to the discovery of broadly neutralizing antibodies. METHODS: We employed a highly complex combinatorial protein library derived from a 5 kDa albumin-binding domain scaffold, fused with support protein of total 38 kDa, to screen for binders of broadly neutralizing antibody VRC01 paratope. The most specific binders were used for immunization of experimental mice to elicit Env-specific antibodies and to test their neutralization activity using a panel of HIV-1 clade C and B pseudoviruses. FINDINGS: Three most specific binders designated as VRA017, VRA019, and VRA177 exhibited high specificity to VRC01 antibody. Immunized mice produced Env-binding antibodies which neutralize eight of twelve HIV-1 Tier 2 pseudoviruses. Molecular modelling revealed a shape complementarity between VRA proteins and a part of VRC01 gp120 interacting surface. INTERPRETATION: This strategy based on the identification of protein replicas of broadly neutralizing antibody paratope represents a novel approach in HIV-1 vaccine development. This approach is not affected by low immunogenicity of neutralization-sensitive epitopes, variability, and unique biochemical properties of HIV-1 Env used as a crucial antigen in the majority of contemporary tested vaccines. FUND: Czech Health Research Council 15-32198A, Ministry of Health, Czech Republic.

• MeSH
• antigeny virové chemie   imunologie   MeSH
• epitopy chemie   imunologie   MeSH
• HIV infekce imunologie   virologie   MeSH
• HIV obalový protein gp120 imunologie   MeSH
• HIV protilátky krev   imunologie   MeSH
• HIV-1 imunologie   MeSH
• imunoglobulin G krev   imunologie   MeSH
• konformace proteinů MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• molekulární modely MeSH
• myši MeSH
• neutralizující protilátky krev   imunologie   MeSH
• sekvence aminokyselin MeSH
• vakcíny proti AIDS imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

We are reporting the first case of lymphogranuloma venereum in women in East-Central Europe. A 22-year-old heterosexual woman attended our department of venereology. She complained about a burning sensation in the urethra and vaginal discharge. Many tests were performed, and lymphogranuloma venereum, syphilis, gonorrhea, chlamydial urethritis and cervicitis, genital herpes, genital warts, and hepatitis C were diagnosed. Lymphogranuloma venereum was originally endemic in tropical and subtropical areas, but since 2003, outbreaks of this infection have been reported in North America, Europe, and Australia in men who have sex with men (MSM) community. To date, all cases of lymphogranuloma venereum in the Czech Republic appeared in men, predominantly in HIV-positive MSM. There are not many evidences about lymphogranuloma venereum (LGV) in women in developed countries. This report underlines the need for awareness of lymphogranuloma venereum in women among gynecologists, venereologists, and other physicians not only in Western Europe, but across all European countries.

• MeSH
• Chlamydia trachomatis klasifikace   genetika   izolace a purifikace   MeSH
• dospělí MeSH
• HIV infekce virologie   MeSH
• koinfekce mikrobiologie   virologie   MeSH
• lidé MeSH
• lymphogranuloma venereum mikrobiologie   MeSH
• mladý dospělý MeSH
• uretra mikrobiologie   MeSH
• vagina mikrobiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Geografické názvy
• Česká republika MeSH