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https://www.readbyqxmd.com/read/28429756/a-non-canonical-binding-interface-in-the-crystal-structure-of-hiv-1-gp120-core-in-complex-with-cd4
#1
Liang-Wei Duan, Hui Zhang, Meng-Ting Zhao, Ji-Xue Sun, Wen-Li Chen, Jian-Ping Lin, Xin-Qi Liu
Numerous crystal structures of HIV gp120 have been reported, alone or with receptor CD4 and cognate antibodies; however, no sole gp120/CD4 complex without stabilization by an antibody is available. Here, we report a crystal structure of the gp120/CD4 complex without the aid of an antibody from HIV-1 CRF07_BC, a strain circulating in China. Interestingly, in addition to the canonical binding surface, a second interacting interface was identified. A mutagenesis study on critical residues revealed that the stability of this interface is important for the efficiency of Env-mediated membrane fusion...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424253/identification-of-acute-hiv-1-infection-by-hologic-aptima-hiv-1-rna-qualitative-assay
#2
Mark M Manak, Leigh Anne Eller, Jennifer Malia, Linda L Jagodzinski, Rapee Trichavaroj, Joseph Oundo, Cornelia Lueer, Fatim Cham, Mark de Souza, Nelson L Michael, Merlin L Robb, Sheila A Peel
The Hologic Aptima HIV-1 Qualitative RNA assay was used in a rigorous screening approach designed to identify individuals at the earliest stage of HIV-1 infection for enrollment into subsequent studies of cellular and viral events in early infection (RV217/Early Capture HIV Cohort - ECHO Study). Volunteers at high risk of HIV-1 infection were recruited from study sites in Thailand, Tanzania, Uganda and Kenya with high HIV-1 prevalence rates among the populations examined. Small volume blood samples were collected by finger-stick at twice-weekly intervals and tested by Aptima...
April 19, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28423342/a-broadly-neutralizing-antibody-targets-the-dynamic-hiv-envelope-trimer-apex-via-a-long-rigidified-and-anionic-%C3%AE-hairpin-structure
#3
Jeong Hyun Lee, Raiees Andrabi, Ching-Yao Su, Anila Yasmeen, Jean-Philippe Julien, Leopold Kong, Nicholas C Wu, Ryan McBride, Devin Sok, Matthias Pauthner, Christopher A Cottrell, Travis Nieusma, Claudia Blattner, James C Paulson, Per Johan Klasse, Ian A Wilson, Dennis R Burton, Andrew B Ward
Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are prophylactic and therapeutic agents. Some of the most potent bnAbs target a quaternary epitope at the apex of the surface HIV envelope (Env) trimer. Using cryo-electron microscopy, we solved the atomic structure of an apex bnAb, PGT145, in complex with Env. We showed that the long anionic HCDR3 of PGT145 penetrated between glycans at the trimer 3-fold axis, to contact peptide residues from all three Env protomers, and thus explains its highly trimer-specific nature...
April 18, 2017: Immunity
https://www.readbyqxmd.com/read/28422793/engineering-antibody-like-inhibitors-to-prevent-and-treat-hiv-1-infection
#4
Matthew R Gardner, Michael Farzan
PURPOSE OF REVIEW: Here we discuss recently developed HIV-1 entry inhibitors that can target multiple epitopes on the HIV-1 envelope glycoprotein (Env), with an emphasis on eCD4-Ig. Some of these inhibitors are more potent and broader than any single antibody characterized to date. We also discuss the use of recombinant adeno-associated virus (rAAV) vectors as a platform for long-term expression of these inhibitors. RECENT FINDINGS: Much of the exterior of HIV-1 Env can be targeted by broadly neutralizing antibodies (bNAbs)...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422787/how-hiv-1-entry-mechanism-and-broadly-neutralizing-antibodies-guide-structure-based-vaccine-design
#5
Marie Pancera, Anita Changela, Peter D Kwong
PURPOSE OF REVIEW: An HIV-1 vaccine that elicits broadly neutralizing antibodies (bNAbs) remains to be developed. Here, we review how knowledge of bNAbs and HIV-1 entry mechanism is guiding the structure-based design of vaccine immunogens and immunization regimens. RECENT FINDINGS: Isolation of bNAbs from HIV-1-infected donors has led to an unprecedented understanding of the sites of vulnerability that these antibodies target on the HIV-1 envelope (Env) as well as of the immunological pathways that these antibody lineages follow to develop broad and potent neutralization...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28422785/role-of-nonneutralizing-antibodies-in-vaccines-and-or-hiv-infected-individuals
#6
Luzia Mayr, Bin Su, Christiane Moog
PURPOSE OF REVIEW: Increased body of evidence gathered over time indicate that antibodies are capable of many inhibitory mechanisms, virus neutralization being just one of them. Nonneutralizing antibodyactivities interfering with HIV replication can also lead to a decrease in viral load and even in-vivo protection. RECENT FINDINGS: It was previously believed that neutralizing antibodies can achieve sterilizing protection mainly by using their neutralization capacities against the infecting virus directly at the portal of virus entry...
May 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28420822/re-entry-and-related-predictors-among-hiv-infected-clients-receiving-methadone-maintenance-treatment-in-guangdong-province-china
#7
Xiaofeng Luo, Xiao Gong, Peizhen Zhao, Xia Zou, Wen Chen, Li Ling
This study examined the re-entry characteristics and related predictors among HIV-infected methadone maintenance treatment (MMT) clients in Guangdong, China. Data on HIV-infected MMT clients was obtained from the clinic MMT registration system in Guangdong. Of the 653 participants, only 9.0% remained in the MMT program until the end of the study. For the drop-outs, 70.0% returned to MMT at least once by the end of the study. Re-entry was independently associated with marital status (ORnever married = 2.24, 95% CI: 1...
April 18, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/28410420/comparison-of-cell-based-assays-for-the-identification-and-evaluation-of-competitive-cxcr4-inhibitors
#8
Anneleen Van Hout, Thomas D'huys, Merel Oeyen, Dominique Schols, Tom Van Loy
The chemokine receptor CXCR4 is activated by its unique chemokine ligand CXCL12 and regulates many physiological and developmental processes such as hematopoietic cell trafficking. CXCR4 is also one of the main co-receptors for human immunodeficiency virus (HIV) entry. Dysfunction of the CXCL12/CXCR4 axis contributes to several human pathologies, including cancer and inflammatory diseases. Consequently, inhibition of CXCR4 activation is recognized as an attractive target for therapeutic intervention. In this regard, numerous agents modifying CXCR4 activity have been evaluated in in vitro experimental studies and pre-clinical models...
2017: PloS One
https://www.readbyqxmd.com/read/28408475/regulation-of-human-immunodeficiency-virus-type-1-hiv-1-mrna-translation
#9
REVIEW
Laura Hidalgo, Chad M Swanson
Human immunodeficiency virus type 1 (HIV-1) mRNA translation is a complex process that uses the host translation machinery to synthesise viral proteins. Several mechanisms for HIV-1 mRNA translation initiation have been proposed including (1) cap-dependent, eIF4E-dependent, (2) cap-dependent, cap-binding complex-dependent, (3) internal ribosome entry sites, and (4) ribosome shunting. While these mechanisms promote HIV-1 mRNA translation in the context of in vitro systems and subgenomic constructs, there are substantial knowledge gaps in understanding how they regulate viral protein production in the context of full-length virus infection...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28405607/chemoattractant-mediated-leukocyte-trafficking-enables-hiv-dissemination-from-the-genital-mucosa
#10
Maud Deruaz, Thomas T Murooka, Sophina Ji, Marc A Gavin, Vladimir D Vrbanac, Judy Lieberman, Andrew M Tager, Thorsten R Mempel, Andrew D Luster
HIV vaginal transmission accounts for the majority of newly acquired heterosexual infections. However, the mechanism by which HIV spreads from the initial site of viral entry at the mucosal surface of the female genital tract to establish a systemic infection of lymphoid and peripheral tissues is not known. Once the virus exits the mucosa it rapidly spreads to all tissues, leading to CD4(+) T cell depletion and the establishment of a viral reservoir that cannot be eliminated with current treatments. Understanding the molecular and cellular requirements for viral dissemination from the genital tract is therefore of great importance, as it could reveal new strategies to lengthen the window of opportunity to target the virus at its entry site in the mucosa where it is the most vulnerable and thus prevent systemic infection...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28399349/sexually-transmitted-infections-prevalence-knowledge-and-behaviours-among-professional-defence-forces-in-estonia-a-pilot-study
#11
David Parker, Kristi Rüütel
OBJECTIVES: Our study assessed sexually transmitted infections (STI) occurrence and risk behaviours from a sample of the defence forces of Estonia. Previous research on military personnel yields various results on the prevalence of STIs and high risk behaviours. The increasing recognition of high risk behaviours among military personnel is evident given increased programmes that focus on education of drug use and risky sexual behaviours. Many militaries conduct routine, periodic screening for diseases such as HIV and viral hepatitis at entry and pre-foreign deployment...
March 2017: Central European Journal of Public Health
https://www.readbyqxmd.com/read/28395249/opioid-users-with-comorbid-hepatitis-c-spent-more-time-in-agonist-therapy-a-6-year-observational-study-in-taiwan
#12
Horng-Maw Chen, Tsung-Hsueh Lu, Kun-Chia Chang, Kuan-Ying Lee, Ching-Ming Cheng
BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent among opioid agonist therapy (OAT) patients, but little is known about long-term OAT use among this population. METHODS: Subjects diagnosed as opioid dependence were recruited from Mar. 2006 to Jul. 2008 in a psychiatry center in southern Taiwan with the OAT censored in 2012, and their socio-demographics, drug use characteristics, and markers of blood-borne infection were assessed at entry. Correlates with HCV infection and OAT retention were analyzed by multivariate logistic regression...
March 31, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28390972/targeting-cell-surface-hiv-1-env-protein-to-suppress-infectious-virus-formation
#13
Arangassery Rosemary Bastian, Charles G Ang, Kantharaju Kamanna, Farida Shaheen, Yu-Hung Huang, Karyn McFadden, Caitlin Duffy, Lauren D Bailey, Ramalingam Venkat Kalyana Sundaram, Irwin Chaiken
HIV-1 Env protein is essential for host cell entry, and targeting Env remains an important antiretroviral strategy. We previously found that a peptide triazole thiol KR13 and its gold nanoparticle conjugate AuNP-KR13 directly and irreversibly inactivate the virus by targeting the Env protein, leading to virus gp120 shedding, membrane disruption and p24 capsid protein release. Here, we examined the consequences of targeting cell-surface Env with the virus inactivators. We found that both agents led to formation of non-infectious virus from transiently transfected HEK293T cells...
April 6, 2017: Virus Research
https://www.readbyqxmd.com/read/28388673/proteolysis-of-mature-hiv-1-p6-gag-protein-by-the-insulin-degrading-enzyme-ide-regulates-virus-replication-in-an-env-dependent-manner
#14
Friedrich Hahn, Adrian Schmalen, Christian Setz, Melanie Friedrich, Stefan Schlößer, Julia Kölle, Robert Spranger, Pia Rauch, Kirsten Fraedrich, Tatjana Reif, Julia Karius-Fischer, Ashok Balasubramanyam, Petra Henklein, Torgils Fossen, Ulrich Schubert
There is a significantly higher risk for type II diabetes in HIV-1 carriers, albeit the molecular mechanism for this HIV-related pathology remains enigmatic. The 52 amino acid HIV-1 p6 Gag protein is synthesized as the C-terminal part of the Gag polyprotein Pr55. In this context, p6 promotes virus release by its two late (L-) domains, and facilitates the incorporation of the viral accessory protein Vpr. However, the function of p6 in its mature form, after proteolytic release from Gag, has not been investigated yet...
2017: PloS One
https://www.readbyqxmd.com/read/28388286/understanding-the-drivers-of-interprofessional-collaborative-practice-among-hiv-primary-care-providers-and-case-managers-in-hiv-care-programmes
#15
Heather A Mavronicolas, Fabienne Laraque, Arti Shankar, Claudia Campbell
Care coordination programmes are an important aspect of HIV management whose success depends largely on HIV primary care provider (PCP) and case manager collaboration. Factors influencing collaboration among HIV PCPs and case managers remain to be studied. The study objective was to test an existing theoretical model of interprofessional collaborative practice and determine which factors play the most important role in facilitating collaboration. A self-administered, anonymous mail survey was sent to HIV PCPs and case managers in New York City...
May 2017: Journal of Interprofessional Care
https://www.readbyqxmd.com/read/28387814/grey-and-white-matter-abnormalities-in-treated-hiv-disease-and-their-relationship-to-cognitive-function
#16
Jonathan Underwood, James H Cole, Matthan Caan, Davide De Francesco, Robert Leech, Rosan A van Zoest, Tanja Su, Gert J Geurtsen, Ben A Schmand, Peter Portegies, Maria Prins, Ferdinand W N M Wit, Caroline A Sabin, Charles Majoie, Peter Reiss, Alan Winston, David J Sharp
Background: Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people-living-with-HIV. We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multi-modal neuroimaging from the Co-morBidity in Relation to AIDS (COBRA) cohort. Methods: Cognitive function, brain tissue volumes and white matter microstructure were assessed in 134 HIV-positive patients and 79 controls...
April 6, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28386256/host-immune-responses-in-hiv-1-infection-the-emerging-pathogenic-role-of-siglecs-and-their-clinical-correlates
#17
REVIEW
Joanna Mikulak, Clara Di Vito, Elisa Zaghi, Domenico Mavilio
A better understanding of the mechanisms employed by HIV-1 to escape immune responses still represents one of the major tasks required for the development of novel therapeutic approaches targeting a disease still lacking a definitive cure. Host innate immune responses against HIV-1 are key in the early phases of the infection as they could prevent the development and the establishment of two hallmarks of the infection: chronic inflammation and viral reservoirs. Sialic acid-binding immunoglobulin-like lectins (Siglecs) belong to a family of transmembrane proteins able to dampen host immune responses and set appropriate immune activation thresholds upon ligation with their natural ligands, the sialylated carbohydrates...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28381579/reverse-transcription-mechanically-initiates-hiv-1-capsid-disassembly
#18
Sanela Rankovic, Janani Varadarajan, Ruben Ramalho, Christopher Aiken, Itay Rousso
The HIV-1 core consists of the viral genomic RNA and several viral proteins encased within a conical capsid. Following cell entry, the core disassembles in a process termed uncoating. Although HIV-1 uncoating has been linked to reverse transcription of the viral genome in target cells, the mechanism by which uncoating is initiated is unknown. Using time-lapse atomic force microscopy, we analyzed the morphology and physical properties of isolated HIV-1 cores during the course of reverse transcription in vitro We find that, during an early stage of reverse transcription the pressure inside the capsid increases, reaching a maximum after 7 hours...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28381571/discovery-of-novel-small-molecule-inhibitors-of-lim-domain-kinase-for-inhibiting-hiv-1
#19
Fei Yi, Jia Guo, Deemah Dabbagh, Mark Spear, Sijia He, Kylene Kehn-Hall, Jacque Fontenot, Yan Yin, Mathieu Bibian, Chul Min Park, Ke Zheng, HaJeung Park, Veronica Soloveva, Dima Gharaibeh, Cary Retterer, Rouzbeh Zamani, Margaret L Pitt, John Naughton, Yongjun Jiang, Hong Shang, Ramin M Hakami, Binhua Ling, John A T Young, Sina Bavari, Xuehua Xu, Yangbo Feng, Yuntao Wu
A dynamic actin cytoskeleton is necessary for viral entry, intracellular migration, and virion release. For HIV-1 infection, during entry, the virus triggers early actin activity through hijacking chemokine coreceptor signaling which activates a host dependency factor cofilin and its kinase, the LIM domain kinase (LIMK). Although knockdown of human LIMK1 with shRNA inhibits HIV infection, no specific small molecule inhibitor of LIMK was available. Here we describe the design and discovery of novel classes of small molecule inhibitors of LIMK for inhibiting HIV infection...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28381554/dna-mutagenic-activity-and-capacity-for-hiv-1-restriction-of-the-cytidine-deaminase-apobec3g-depends-on-whether-dna-or-rna-binds-to-tyrosine-315
#20
Bogdan Polevoda, Rebecca Joseph, Alan E Friedman, Ryan P Bennett, Rebecca Greiner, Thareendra De Zoysa, Ryan A Stewart, Harold C Smith
APOBEC3G (A3G) belongs to the AID/APOBEC protein family of cytidine deaminases (CDA) that bind to nucleic acids. A3G mutates the HIV genome by deamination of dC to dU, leading to accumulation of virus-inactivating mutations. Binding to cellular RNAs inhibits A3G binding to substrate single-stranded (ss) DNA and CDA activity. RNA and ssDNA bind to the same three A3G tryptic peptides (amino acids 181-194, 314-320, and 345-374) that form parts of a continuously exposed protein surface extending from the catalytic domain in the C-terminus of A3G to its N-terminus...
April 5, 2017: Journal of Biological Chemistry
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