Breaking News
March 21, 2019 - MIT announces creation of the Alana Down Syndrome Center
March 21, 2019 - Next-generation LVAD device clinically superior, safer for heart failure patients
March 21, 2019 - Allergan Announces FDA Approval of Avycaz (ceftazidime and avibactam) for Pediatric Patients
March 21, 2019 - Mutations in noncoding genes could play big role in regulating cancer, study finds
March 21, 2019 - A medical student’s thoughts on Match Day
March 21, 2019 - Are eggs good or bad for you?
March 21, 2019 - New analysis reveals precision oncology insights for colorectal cancer
March 21, 2019 - Pollutants appear to weaken immune system and increase pathogen virulence
March 21, 2019 - Researchers develop and validate scale for rating severity of mononucleosis
March 21, 2019 - Scientists identify generation of key immune response in mice on introducing solid food
March 21, 2019 - New nanomaterial could restore internal structure of damaged bones
March 21, 2019 - Selective destruction of prostate tumor as effective as complete prostate removal
March 21, 2019 - 2011 to 2015 Saw Increase in Psychiatric ED Visits for Youth
March 21, 2019 - Tapeworm drug targets common vulnerability in tumor cells
March 21, 2019 - Off the beaten path for global health residency
March 21, 2019 - European Parliament’s report calls on EU to develop policies to regulate endocrine-disrupting chemicals
March 21, 2019 - Women with undiagnosed diabetes in pregnancy more likely to experience stillbirths
March 21, 2019 - Fish consumption can help prevent asthma, study reveals
March 21, 2019 - Royal Holloway professors to lead new to research into curing Neurofibromatosis type 1
March 21, 2019 - NSF offers grant to improve treatment approaches for pelvic organ prolapse
March 21, 2019 - Your Apple Watch Might Help Spot a Dangerous Irregular Heartbeat
March 21, 2019 - Research team uncovers critical new clues about what goes awry in autistic brains
March 21, 2019 - From March Madness to medicine with help from mentors
March 21, 2019 - Mental health disorders among young adults may be on the increase
March 21, 2019 - New study examines smarter automatic defibrillator
March 21, 2019 - UC Riverside research shows how natural selection favors cheaters
March 21, 2019 - Mother’s diet during pregnancy can impact lung-specific genes of her offspring
March 21, 2019 - AeroForm Tissue Expanders makes breast reconstruction after mastectomy more comfortable
March 21, 2019 - New project focuses on creating more responsive, intuitive prosthetics
March 21, 2019 - New case study describes adolescent patient with rapid-onset schizophrenia and Bartonella infection
March 21, 2019 - Umass Amherst food scientist honored with 2019 Young Scientist Research Award
March 21, 2019 - Smell of skin could lead to early diagnosis for Parkinson’s
March 21, 2019 - Difference in brain connectivity may explain autism spectrum disorder
March 21, 2019 - Untangling the microbiome — with statistics
March 21, 2019 - Human microbiome metabolites enhance colon injury by enterohemorrhagic E. coli, study shows
March 21, 2019 - Written media can improve citizens’ understanding of palliative care
March 21, 2019 - New research aims to find how asthma symptoms are aggravated
March 21, 2019 - New $9.7 million NIH grant project seeks to improve hearing restoration
March 21, 2019 - Researchers measure brain metabolite levels in people with mild memory problems
March 21, 2019 - FDA approves first drug for treatment of postpartum depression in adult women
March 20, 2019 - Gene editing and designer babies experiments face global moratorium
March 20, 2019 - Major scientific study of wound care dressings wins ‘Best Clinical or Preclinical Research Award’
March 20, 2019 - Biohaven Enrolls First Patient In Phase 3 Generalized Anxiety Disorder (GAD) Trial Of Troriluzole
March 20, 2019 - Big data study identifies drugs that increase risk of psychosis in youth with ADHD
March 20, 2019 - Mystery novel and dream spur key scientific insight into heart defect | News Center
March 20, 2019 - Study measures impact of policies designed to reduce air pollution in two mega-cities
March 20, 2019 - Mild sleep apnea during pregnancy changes sugar levels and may affect infant growth patterns
March 20, 2019 - SSB and Novasep collaborate to develop new membrane chromatography systems
March 20, 2019 - Leaky valve repair improves quality of life in heart failure patients
March 20, 2019 - Diattenuation Imaging offers structural information of difficult to access brain regions
March 20, 2019 - Early sports specialization linked to increased injury rates during athletic career
March 20, 2019 - Study brings clarity about milk intake for children with Duarte galactosemia
March 20, 2019 - Allergan Announces FDA Acceptance of New Drug Application for Ubrogepant for the Acute Treatment of Migraine
March 20, 2019 - Maternal smoking during pregnancy increases risk of ADHD among offspring up to three-fold
March 20, 2019 - Pioneering pediatric kidney transplant surgeon Oscar Salvatierra dies at 83 | News Center
March 20, 2019 - F.D.A. Approves First Drug for Postpartum Depression
March 20, 2019 - TB remains a major public health challenge in the European region
March 20, 2019 - Most pills contain common allergens, warn experts
March 20, 2019 - Researchers discover previously unknown mechanism by which cells can sense oxygen
March 20, 2019 - World’s leading source of data on diagnosis, treatments for aortic dissection
March 20, 2019 - Breast cancer relapse predictor may soon be a reality
March 20, 2019 - Researchers identify origin of chronic pain in humans
March 20, 2019 - Two-drug combinations containing calcium channel blocker significantly lowers BP
March 20, 2019 - King’s scientists to monitor air quality exposure of 250 children
March 20, 2019 - Active substance from plant could turn into a ray of hope against eye tumors
March 20, 2019 - Preventative cardioverter defibrillator implantation is of little benefit to kidney dialysis patients
March 20, 2019 - New method based on neurofeedback may reduce anxiety
March 20, 2019 - Study explores whether alcohol consumption can have an effect on arthritis
March 20, 2019 - Merck to collaborate with GenScript for plasmid and virus manufacturing in China
March 20, 2019 - FDA Approves Zulresso (brexanolone) for the Treatment of Postpartum Depression
March 20, 2019 - Study examines long-term opioid use in patients with severe osteoarthritis
March 20, 2019 - Retired Stanford professor Edward Rubenstein, pioneer in intensive care medicine, dies at 94 | News Center
March 20, 2019 - Aaron Diamond AIDS Research Center to Join Columbia University
March 20, 2019 - Call for halt to human gene editing and designer babies experiments
March 20, 2019 - Study illuminates how hot spots of genetic variation evolved in the human genome
March 20, 2019 - Roundworm study suggests alternatives for treatment of schizophrenia
March 20, 2019 - Sphingotec reports new applications of bio-ADM at 39th ISICEM
March 20, 2019 - Preventing falls through free community-based screenings for older adults
March 20, 2019 - AAOS: Supplement Use Low in Patients With Osteoporosis, Hip Fracture
March 20, 2019 - Does intensive blood pressure control reduce dementia?
Study finds specific function of HIV protein that slows viral spread in early stages of infection

Study finds specific function of HIV protein that slows viral spread in early stages of infection

image_pdfDownload PDFimage_print

A study from a Massachusetts General Hospital (MGH) research team has identified the specific function of a protein found in HIV and related viruses that appears to slow down viral spread in the earliest stages of infection. But they also found that, after initially slowing down the spread of infection, that function may help the virus survive later on by evading the immune response. Their report has been published in Cell Host & Microbe.

“HIV uses several proteins with a number of functions predicted to change the migratory patterns of infected cells,” says Thorsten Mempel, MD, PhD, of the MGH Center for Immunology and Inflammatory Diseases, senior author of the report. “Our investigation identified a particular function of the protein Nef as responsible for disrupting the ability of infected T cells to migrate, slowing the rate at which the virus initially spreads after infection. However, that same function allowed the virus to persist at a later time when the adaptive immune response – especially the response of cytotoxic ‘killer’ T cells – has become activated. These findings suggest that this function of Nef evolved to help HIV evade the immune response but at the expense of initially slower spread in an infected animal.”

Recent studies by Mempel’s team and others have suggested that – in contrast to the conventional view that HIV spreads throughout the body as free viral particles – the virus can be transported by infected T cells that travel through tissues and the circulatory system and then spread the infection by direct contact with uninfected cells. Since Nef has previously been shown both to downregulate the function of several proteins involved in signal transduction and to disrupt processes thought to drive cellular migration, the MGH team took a detailed look at exactly how Nef and other HIV proteins exert their effects on the motility of infected T cells.

Their experiments in mice with key elements of a human immune system – the only animal model capable of being infected with HIV – supported previous findings that Nef reduces the migration of infected cells by disrupting the assembly and disassembly of a protein called actin into branched filaments. Actin filaments support the shape of cells and enable them to move by pushing the outer membrane out on one side while retracting the membrane on the other end. This function of Nef is carried out through the interaction of a “hydrophobic patch” – a group of water-repelling amino acids closely spaced on the surface of the protein – with a group of cellular proteins including an enzyme called PAK2.

In the first weeks after female mice were vaginally inoculated with two strains of HIV – one with a mutated form of Nef in which the hydrophobic patch is disrupted and one unmutated strain – the Nef-mutant strain became dominant, implying that T cells infected with that strain had spread the infection more rapidly than those with the unmutated strain. But over time the mutant strain disappeared and the unmutated strain of HIV became dominant, coinciding with increased activity of the anti-HIV cytotoxic T cell response. The authors also found that the benefit to viral survival conferred by the hydrophobic patch on the unmutated form of Nef was not seen in cellular studies, suggesting that it had developed in response to the immune system pressures present in a live animal.

“We know that other functions of Nef appear to have evolved primarily to help HIV evade the immune response, so it makes sense that disruption of the actin cytoskeleton serves a similar purpose,” says Mempel, who is an associate professor of Medicine at Harvard Medical School. “The fact that this appears only in living animals clearly suggests that important biological properties of the virus are not apparent in the cell culture systems traditionally used to study HIV. This means there is still a lot to discover about what HIV can do and what its potential weaknesses are. Importantly, if it becomes possible to target the ability of Nef to disrupt the cytoskeleton, we may be able to increase the vulnerability of HIV to antiviral treatment strategies, such as vaccination or broadly neutralizing antibodies.”

Source:

https://www.massgeneral.org/about/pressrelease.aspx?id=2336

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Actin, AIDS, Antibodies, Cancer, Cell, Cell Culture, Cytoskeleton, Enzyme, Genomic, Health Care, HIV, HIV/AIDS, Hospital, Imaging, Immune Response, Immune System, Immunology, Medical Imaging, Medical School, Medicine, Protein, Research, Virus, Viruses

Tagged with:

About author

Related Articles