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HIV and retrovirus

Jingyou Yu, Shan-Lu Liu
Interferon inducible transmembrane proteins (IFITMs) are one of several IFN-stimulated genes (ISGs) that restrict entry of enveloped viruses, including flaviviruses, filoviruses and retroviruses. It has been recently reported that in U87 glioblastoma cells IFITM proteins inhibit HIV-1 entry in a co-receptor-dependent manner, that is, IFITM1 is more inhibitory on CCR5 tropic HIV-1 whereas IFITM2/3 confers a greater suppression of CXCR4 counterparts. However, how entry of HIV-1 with distinct co-receptor usage is modulated by different IFITM orthologs in physiologically relevant CD4⁺ T cells and monocytes/macrophages has not been investigated in detail...
August 7, 2018: Viruses
Kristina Meier, Ananda Ayyappan Jaguva Vasudevan, Zeli Zhang, Ariane Bähr, Georg Kochs, Dieter Häussinger, Carsten Münk
Human myxovirus resistance protein B (hMXB) is a restriction factor of HIV-1 that also inhibits a variety of retroviruses. However, hMXB is not antiviral against equine infectious anemia virus (EIAV). We show here that equine MX2 (eMX2) potently restricts EIAV in vitro. Additionally, eMX2 inhibits HIV-1 and other lentiviruses, including murine leukemia virus. Previously, it was reported that hMXB repression is reduced in hMXB Δ1-25, but not in GTP-binding mutant K131A and GTP-hydrolysis mutant T151A. In contrast to this phenomenon, our study indicates that eMX2 restriction is not diminished in eMX2 Δ1-25, but is in eMX2 K127A and T147A, which correspond to hMXB K131A and T151A, respectively...
August 3, 2018: Virology
Kunchok Dorjee, Tsering Choden, Sanjiv M Baxi, Craig Steinmaus, Arthur L Reingold
BACKGROUND: Abacavir's potential to cause cardiovascular disease (CVD) among people living with HIV (PLWH) is debated. We conduct a systematic review and meta-analyses to assess CVD risk from recent and cumulative abacavir exposure. METHODS: Search of Medline, Embase, Web of Science, abstracts from Conference on Retroviruses and Opportunistic Infections, International AIDS Society/AIDS Conferences and bibliographies of review articles to identify research studies published through 2018 on CVD risk associated with abacavir exposure among PLWH...
July 21, 2018: International Journal of Antimicrobial Agents
Ingrid Eshun-Wilson, Mbah P Okwen, Marty Richardson, Tihana Bicanic
BACKGROUND: There remains uncertainty about the optimum timing of antiretroviral therapy (ART) initiation in HIV-positive people with cryptococcal meningitis. This uncertainty is the result of conflicting data on the mortality risk and occurrence of immune reconstitution inflammatory syndrome (IRIS) when ART is initiated less than four weeks after cryptococcal meningitis treatment is commenced. OBJECTIVES: To compare the outcomes of early initiation of ART (less than four weeks after starting antifungal treatment) versus delayed initiation of ART (four weeks or more after starting antifungal treatment) in HIV-positive people with concurrent cryptococcal meningitis...
July 24, 2018: Cochrane Database of Systematic Reviews
Masha Maharaj, Nisaar Korowlay
Skeletal involvement occurs in 30%-70% of all cancer patients, with breast cancer (BC) being the leading cause for bone metastases in women and prostate cancer in men followed by lung cancer. Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome. It is yet unknown what is the impact of HIV to the onset and progression of bone disease in BC. The purpose of the study was to determine the association of HIV infection and skeletal metastases in BC using skeletal scintigraphy...
July 2018: World Journal of Nuclear Medicine
Annarosaria De Vito, Massimo Lazzaro, Ilaria Palmisano, Davide Cittaro, Michela Riba, Dejan Lazarevic, Makoto Bannai, Davide Gabellini, Maria Vittoria Schiaffino
In a variety of species, reduced food intake, and in particular protein or amino acid (AA) restriction, extends lifespan and healthspan. However, the underlying epigenetic and/or transcriptional mechanisms are largely unknown, and dissection of specific pathways in cultured cells may contribute to filling this gap. We have previously shown that, in mammalian cells, deprivation of essential AAs (methionine/cysteine or tyrosine) leads to the transcriptional reactivation of integrated silenced transgenes, including plasmid and retroviral vectors and latent HIV-1 provirus, by a process involving epigenetic chromatic remodeling and histone acetylation...
2018: PloS One
R M Mackler, M A Lopez, M J Osterhage, K E Yoder
Retroviruses have two essential activities: reverse transcription and integration. The viral protein integrase (IN) covalently joins the viral cDNA genome to the host DNA. Prototype foamy virus (PFV) IN has become a model of retroviral intasome structure. However, this retroviral IN has not been well-characterized biochemically. Here we compare PFV IN to previously reported HIV-1 IN activities and discover significant differences. PFV IN is able to utilize the divalent cation calcium during strand transfer while HIV-1 IN is not...
July 13, 2018: Biochemical and Biophysical Research Communications
Ann A Kiessling
Thanks to effective anti-HIV medications, deaths from acquired immunodeficiency disease (AIDS) have plummeted, although the incidence of new HIV infections has decreased little, approximately 36,000 annually in the USA. The CDC estimates 1.1 million persons, mostly men, are living with HIV in the USA, with approximately 14% unaware they are infected. Since the global blood supply is essentially free of HIV today, infected semen is fueling the pandemic (88% of new infections in the USA), with needle sharing among IV drug abusers (7% of new US infections) and female to male transmission (5% of new infections) accounting for the balance...
July 13, 2018: Journal of Assisted Reproduction and Genetics
Daniel Ivanusic, Heiko Pietsch, Jasper König, Joachim Denner
Immunosuppression by retroviruses including the human immunodeficiency virus-1 (HIV-1) is well known, however the mechanisms how retroviruses induce this immunosuppression is not fully investigated. It was shown that non-infectious retroviral particles as well as retroviral or recombinant retroviral transmembrane envelope (TM) proteins demonstrated immunosuppressive properties. The same was shown for peptides corresponding to a highly conserved domain in the TM protein. This domain is called immunosuppressive (ISU) domain and it induces modulation of the cytokine release of peripheral blood mononuclear cells (PBMCs) from healthy donors...
2018: PloS One
Cindy Buffone, Alicia Martinez-Lopez, Thomas Fricke, Silvana Opp, Marco Severgnini, Ingrid Cifola, Luca Petiti, Stella Frabetti, Katarzyna Skorupka, Kaneil K Zadrozny, Barbie K Ganser-Pornillos, Owen Pornillos, Francesca Di Nunzio, Felipe Diaz-Griffero
HIV-1 displays the unique ability to infect non-dividing cells. The capsid of HIV-1 is the viral determinant for viral nuclear import. To understand the cellular factors involved in the ability of HIV-1 to infect non-dividing cells, we sought to find capsid mutations that allow the virus to infect dividing but not non-dividing cells. Because the interaction of capsid with the nucleoporin protein 153 (Nup153) is important for nuclear import of HIV-1, we solved new crystal structures of hexameric HIV-1 capsid in complex with a Nup153-derived peptide containing a phenylalanine-glycine repeat (FG-repeat), which we used to guide structure-based mutagenesis of the capsid-binding interface...
July 11, 2018: Journal of Virology
Julian Gold, Monica Marta, Ute C Meier, Tove Christensen, David Miller, Daniel Altmann, David Holden, Lucia Bianchi, Rocco Adiutori, David MacManus, Tarek Yousry, Klaus Schmierer, Benjamin Turner, Gavin Giovannoni
BACKGROUND: Although the aetiology of multiple sclerosis (MS) remains elusive, it is clear that Epstein Barr virus (EBV) and possibly other viruses play a role in the pathogenesis of MS. Laboratory evidence suggests that human endogenous retroviruses (HERVs) could also have a role, but no interventional therapy has determined what will happen if HERVs are suppressed. Recent epidemiological evidence indicates patients with HIV infection have a significantly lower risk of developing MS and that HIV antiretroviral therapies may be coincidentally inhibiting HERVs, or other retroelements, that could be implicated in MS...
June 28, 2018: Multiple Sclerosis and related Disorders
Espérance Kashala-Abotnes, Daniel Okitundu, Dieudonne Mumba, Michael J Boivin, Thorkild Tylleskär, Desire Tshala-Katumbay
Epidemics of neurodegenerative diseases putatively caused by food toxins have been reported in the tropics with no clear understanding of their pathogenetic mechanisms. These diseases include the disease named Konzo that has been well documented in sub-Sahara Africa, mostly among children and women of childbearing age. Outbreaks of Konzo have occurred in the Democratic Republic of Congo, Mozambique, Tanzania, Central African Republic, Angola, Cameroun, and most recently in Zambia. The main clinical picture consists of a symmetrical, permanent and irreversible spastic paraparesis (motor neuron disease) with no signs of sensory or genitourinary impairments...
July 5, 2018: Brain Research Bulletin
Hsin Chien, Christine I Alston, Richard D Dix
AIDS-related human cytomegalovirus retinitis remains the leading cause of blindness among untreated HIV/AIDS patients worldwide. To study mechanisms of this disease, we use a clinically relevant animal model of murine cytomegalovirus (MCMV) retinitis with retrovirus-induced murine acquired immunodeficiency syndrome (MAIDS) that mimics the progression of AIDS in humans. We found in this model that MCMV infection significantly stimulates ocular suppressor of cytokine signaling (SOCS)1 and SOCS3, host proteins which hinder immune-related signaling by cytokines, including antiviral type I and type II interferons...
July 5, 2018: Journal of Virology
Mirjam Schilling, Lorenzo Bulli, Sebastian Weigang, Laura Graf, Sebastian Naumann, Corinna Patzina, Valentina Wagner, Liane Bauersfeld, Caroline Goujon, Hartmut Hengel, Anne Halenius, Zsolt Ruzsics, Torsten Schaller, Georg Kochs
Herpesvirus infections are highly prevalent in the human population and persist for lifetime. They are often acquired subclinically but potentially progress to life-threatening diseases in immunocompromised individuals. The interferon system is indispensable for the control of herpesviral replication. However, the responsible antiviral effector mechanisms are not well characterized. The type I interferon-induced, human myxovirus resistance 2 ( MX2 ) gene product MxB, a dynamin-like large GTPase, has recently been identified as potent inhibitor of HIV-1...
June 27, 2018: Journal of Virology
Nina Yancheva, Dimitar Strashimirov, Vasil Hrischev, Tatyana Tchervenyakova, Maria Nikolova, Ivaylo Aleksiev
HIV-associated lymphoma was first classified as an AIDS-defining disease by the American Center for Disease Control and Prevention (CDC) in 1985. Non-Hodgkin's lymphomas (NHLs) are frequent malignancies in AIDS patients. The risk of NHL in the case of an underlying HIV infection is estimated to be 100 times greater than in the general population, and it increases with the progression of the retrovirus-related immunosuppression. Cases of HIV-related non-Hodgkin's lymphoma are widely documented in the literature...
June 1, 2018: Le Infezioni in Medicina
Duane P Grandgenett, Hideki Aihara
Integration of the reverse-transcribed viral cDNA into the host's genome is a critical step in the lifecycle of all retroviruses. Retrovirus integration is carried out by integrase (IN), a virus-encoded enzyme that forms an oligomeric 'intasome' complex with both ends of the linear viral DNA to catalyze their concerted insertions into the backbones of the host's DNA. IN also forms a complex with host proteins, which guides the intasome to the host's chromosome. Recent structural studies have revealed remarkable diversity as well as conserved features among the architectures of the intasome assembly from different genera of retroviruses...
2018: Sub-cellular Biochemistry
Robert Craigie
Integration of a DNA copy of the viral genome into host DNA is an essential step in the replication cycle of HIV-1 and other retroviruses and is an important therapeutic target for drugs. DNA integration is catalyzed by the viral integrase protein and proceeds through a series of stable nucleoprotein complexes of integrase, viral DNA ends and target DNA. These nucleoprotein complexes are collectively called intasomes. Retroviral intasomes undergo a series of transitions between initial formation and catalysis of the DNA cutting and joining steps of DNA integration...
2018: Sub-cellular Biochemistry
Yantao Yang, Na Qu, Jie Tan, Muaz N Rushdi, Christopher J Krueger, Antony K Chen
During HIV-1 assembly, the retroviral structural protein Gag forms an immature capsid, containing thousands of Gag molecules, at the plasma membrane (PM). Interactions between Gag nucleocapsid (NC) and viral RNA (vRNA) are thought to drive assembly, but the exact roles of these interactions have remained poorly understood. Since previous studies have shown that Gag dimer- or trimer-forming mutants (GagZiL ) lacking an NC domain can form immature capsids independent of RNA binding, it is often hypothesized that vRNA drives Gag assembly by inducing Gag to form low-ordered multimers, but is dispensable for subsequent assembly...
June 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Spyridon Stavrou, Alexya N Aguilera, Kristin Blouch, Susan R Ross
Host recognition of viral nucleic acids generated during infection leads to the activation of innate immune responses essential for early control of virus. Retrovirus reverse transcription creates numerous potential ligands for cytosolic host sensors that recognize foreign nucleic acids, including single-stranded RNA (ssRNA), RNA/DNA hybrids, and double-stranded DNA (dsDNA). We and others recently showed that the sensors cyclic GMP-AMP synthase (cGAS), DEAD-box helicase 41 (DDX41), and members of the Aim2-like receptor (ALR) family participate in the recognition of retroviral reverse transcripts...
June 5, 2018: MBio
Gatikrushna Singh, Brittany D Rife, Bradley Seufzer, Marco Salemi, Aaron Rendahl, Kathleen Boris-Lawrie
Precise stoichiometry of genome-length transcripts and alternatively spliced mRNAs is a hallmark of retroviruses. We discovered short, guanosine and adenosine sequence motifs in the 5'untranslated region of several retroviruses and ascertained the reasons for their conservation using a representative lentivirus and genetically simpler retrovirus. We conducted site-directed mutagenesis of the GA-motifs in HIV molecular clones and observed steep replication delays in T-cells. Quantitative RNA analyses demonstrate the GA-motifs are necessary to retain unspliced viral transcripts from alternative splicing...
May 26, 2018: Nucleic Acids Research
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