CRISPR Eliminates HIV in Live Animals | GEN

 Due to their innate nature to hide away and remain latent for extended periods of time, HIV infections have proven notoriously difficult to eliminate. Yet now, new data released from a research team led by investigators at the Lewis Katz School of Medicine at Temple University (LKSOM) and the University of Pittsburgh shows that HIV DNA can be excised from the genomes of living animals to eliminate further infection. Additionally, the researchers are the first to perform this feat in three different animal models, including a "humanized" model in which mice were transplanted with human immune cells and infected with the virus. Findings from the new study were published recently in Molecular Therapy in an article entitled “In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models.”      published in Molecular therapy



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Brains of HIV-positive elders have less Alzheimer's-linked damage Medical News Today

Elderly people with HIV/AIDS have fewer lesions of Alzheimer's disease in their brains than their HIV-negative peers, new findings presented at Touro College Research Day show.

"The frequency of Alzheimer-type changes in the brains of aging patients with chronic HIV infection and/or AIDS
is lower than in the brains of normal, non-HIV infected patients," said
Dr. Piotr Kozlowski, MD, the study's lead author and Dean of Research
at Touro College of Osteopathic Medicine.

Dr. Kozlowski and his colleagues studied brain tissue from 56 people
with AIDS and from 15 HIV-negative individuals. They obtained the brain
tissue samples from the National NeuroAIDS Tissue Consortium, a network
of four clinical sites across the United States that bank tissue from
people with HIV as well as healthy individuals.

Researchers identify good bacteria that protects against HIV

Researchers at the University of Texas Medical Branch at Galveston by
growing vaginal skin cells outside the body and studying the way they
interact with "good and bad" bacteria, think they may be able to better
identify the good bacteria that protect women from HIV infection and
other sexually transmitted infections.

New studies detail how HIV affects immune system, claim drug exists to block virus

In a last-ditch effort to rid the body of HIV, droves of white bloods cells self-destruct in an explosive mass suicide that drives the progression toward AIDS, a pair of new studies has found.

These fiery deaths attract more unsuspecting cells to come over and help, initiating a domino effect of immune system destruction. The discovery of these mechanisms of cell death has solved a decades-long mystery that has plagued HIV researchers since the emergence of the disease. And researchers claim an existing drug may be able to halt this suicide cascade in its tracks.

The study in Nature identifies the chain reaction and corresponding enzymes involved. The other from Science pinpoints a protein within the white blood cell that sniffs out the viral DNA and tells the cell to pull the trigger on itself. Both were published online Thursday.

Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection Nature

PLOS ONE: Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection

HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against viral invasion. However, apoptosis can be selectively reactivated in HIV-infected cells by chemical agents that interfere with HIV-1 gene expression. We studied two globally used medicines, the topical antifungal ciclopirox and the iron chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both medicines activated apoptosis preferentially in HIV-infected cells, suggesting that the drugs mediate escape from the viral suppression of defensive apoptosis. In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane depolarization, initiating the intrinsic pathway of apoptosis to execution, as evidenced by caspase-3 activation, poly(ADP-ribose) polymerase proteolysis, DNA degradation, and apoptotic cell morphology. In isolate-infected peripheral blood mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug cessation, suggesting elimination of the proviral reservoir. Tests in mice predictive for cytotoxicity to human epithelia did not detect tissue damage or activation of apoptosis at a ciclopirox concentration that exceeded by orders of magnitude the concentration causing death of infected cells. We infer that ciclopirox and deferiprone act via therapeutic reclamation of apoptotic proficiency (TRAP) in HIV-infected cells and trigger their preferential elimination. Perturbations in viral protein expression suggest that the antiretroviral activity of both drugs stems from their ability to inhibit hydroxylation of cellular proteins essential for apoptosis and for viral infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone as prototypes of selectively cytocidal antivirals that eliminate viral infection by destroying infected cells. A drug-based drug discovery program, based on these compounds, is warranted to determine the potential of such agents in clinical trials of HIV-infected patients.

Retinazone inhibits certain blood-borne human viruses including Ebola virus Zaire.

Human hepatitis B and immunodeficiency viruses integrate their retro-transcribed DNA proviruses into the human host genome. Existing antiretroviral drug regimens fail to directly target these intrachromosomal xenogenomes, leading to persistence of viral genetic information. Retinazone (RTZ) constitutes a novel vitamin A-derived (retinoid) thiosemicarbazone derivative with broad-spectrum antiviral activity versus human immunodeficiency, hepatitis C, varicella-zoster and cytomegalo-viruses.

METHODS:

The in vitro inhibitory action of RTZ on HIV-1 strain LAI, human hepatitis B virus strain ayw, HCV-1b strain Con1, enhanced green fluorescent protein-expressing Ebola virus Zaire 1976 strain Mayinga, wild-type Ebola virus Zaire 1976 strain Mayinga, human herpesvirus 6B and Kaposi's sarcoma-associated herpesvirus replication was investigated. The binding of RTZ to human glucocorticoid receptor was determined.

RESULTS:

RTZ inhibits the bloodborne human hepatitis B virus multiplication in vitro by covalent inactivation of intragenic and intraexonic viral glucocorticoid response elements, and, in close analogy, RTZ suppresses HIV-1 multiplication in vitro. RTZ disrupts the multiplication of the bloodborne human hepatitis C and Ebola Zaire viruses at nanomolar concentrations in vitro. RTZ has the capacity to bind to human glucocorticoid receptor, to selectively and covalently bind to intraexonic viral glucocorticoid response elements, and thereby to inactivate human genome-integrated proviral DNA of human hepatitis B and immunodeficiency viruses.

CONCLUSIONS:

RTZ represents the first reported antiviral agent capable of eradicating human immunodeficiency and hepatitis B proviruses from their human host. Furthermore, RTZ represents a potent and efficacious small-molecule in vitro inhibitor of Ebola virus Zaire 1976 strain Mayinga replication.

Researchers show how cells' DNA repair machinery can destroy viruses

A team of researchers based at Johns Hopkins has decoded a system that makes certain types of immune cells impervious to HIV infection. The system's two vital components are high levels of a molecule that becomes embedded in viral DNA like a code written in invisible ink, and an enzyme that, when it reads the code, switches from repairing the DNA to chopping it up into unusable pieces. The researchers, who report the find in the Jan. 21 early edition of the Proceedings of the National Academy of Sciences, say the discovery points toward a new approach to eradicating HIV from the body."


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SIV and the Expanding Virome - The Scientist Magazine®

Pathogenic infection with simian immunodeficiency virus (SIV), a relative of HIV that infects non-human primates, is associated with increased diversity of gastrointestinal virus species in rhesus macaques, according to findings published today (October 11) in Cell. Though previous work has implicated intestinal bacteria in stimulating chronic inflammation, which is believed to promote progression from HIV or SIV infection to AIDS, the new findings suggest that gut viruses may also play a role.

Compound discovered that boosts effect of vaccines against HIV and flu

Oxford University scientists have discovered an adjuvant polymer (polyethyleneimine) that boosts the effect of vaccines against viruses like flu, HIV and herpes in mice.

A safer strategy for targeting AIDS

Scientists at The Scripps Research Institute have discovered a surprisingly simple and safe method to disrupt specific genes within cells. The scientists highlighted the medical potential of the new technique by demonstrating its use as a safer alternative to an experimental gene therapy against HIV infection.The new technique, reported last month in the journal Nature Methods, employs zinc finger nuclease (ZFN) proteins, which can bind and cut DNA at precisely defined locations in the genome. ZFNs are coming into widespread use in scientific experiments and potential disease treatments, but typically are delivered into cells using potentially risky gene therapy methods.

Virus-producing cells determine the host protein profiles of HIV-1 virion cores.

Upon HIV entry into target cells, viral cores are released and rearranged into reverse transcription complexes (RTCs), which support reverse transcription and also protect and transport viral cDNA to the site of integration. RTCs are composed of viral and cellular proteins that originate from both target and producer cells, the latter entering the target cell within the viral core. However, the proteome of HIV-1 viral cores in the context of the type of producer cells has not yet been characterized. RESULTS: We examined the proteomic profiles of the cores purified from HIV-1 NL4-3 virions assembled in Sup-T1 cells (T lymphocytes), PMA and vitamin D3 activated THP1 (model of macrophages, mMPhi), and non-activated THP1 cells (model of monocytes, mMN) and assessed potential involvement of identified proteins in the early stages of infection using gene ontology information and data from genome-wide screens on proteins important for HIV-1 replication. We identified 202 cellular proteins incorporated in the viral cores (T cells: 125, mMPhi: 110, mMN: 90) with the overlap between these sets limited to 42 proteins. The groups of RNA binding (29), DNA binding (17), cytoskeleton (15), cytoskeleton regulation (21), chaperone (18), vesicular trafficking-associated (12) and ubiquitin-proteasome pathway-associated proteins (9) were most numerous. Cores of the virions from SupT1 cells contained twice as many RNA binding proteins as cores of THP1-derived virus, whereas cores of virions from mMPhi and mMN were enriched in components of cytoskeleton and vesicular transport machinery, most probably due to differences in virion assembly pathways between these cells. Spectra of chaperones, cytoskeletal proteins and ubiquitin-proteasome pathway components were similar between viral cores from different cell types, whereas DNA-binding and especially RNA-binding proteins were highly diverse. Western blot analysis showed that within the group of overlapping proteins, the level of incorporation of some RNA binding (RHA and HELIC2) and DNA binding proteins (MCM5 and Ku80) in the viral cores from T cells was higher thanin the cores from both mMPhi and mMN and did not correlate with the abundance of these proteins in virus producing cells. CONCLUSIONS: Profiles of host proteins packaged in the cores of HIV-1 virions depend on the type of virus producing cell. The pool of proteins present in the cores of all virions is likely to contain factors important for viral functions. Incorporation ratio of certain RNA- and DNA-binding proteins suggests their more efficient, non-random packaging into virions in T cells than in mMPhi and mMN.

MicrobeWorld - Cancer drug shocks HIV out of hiding

Awakening the virus from its hiding place may allow its attack and elimination ...........

Bone marrow transplant eliminates signs of HIV infection

Two men with longstanding HIV infections no longer have detectable HIV in their blood cells following bone marrow transplants. The virus was easily detected in blood lymphocytes of both men prior to their transplants but became undetectable by eight months post-transplant. The men, who were treated at Brigham and Women's Hospital (BWH), have remained on anti-retroviral therapy. Their cases will be presented on July 26, 2012 at the International AIDS Conference by Timothy Henrich, MD and Daniel Kuritzkes, MD, physician-researchers in the Division of Infectious Diseases at BWH.

Potent new compound virtually eliminates HIV in cell culture

A new study by scientists on the Florida campus of The Scripps Research Institute shows, in cell culture, a natural compound ( Cortistatin A) can virtually eliminate human immunodeficiency virus (HIV) in infected cells. The compound defines a novel class of HIV anti-viral drugs endowed with the capacity to repress viral replication in acutely and chronically infected cells.

Futurity.org – Sea moss compound flushes out latent HIV

STANFORD (US) — A new collection of compounds—derived from a tiny marine organism—activate hidden reservoirs of HIV that currently make AIDS nearly impossible to eradicate.

Breast milk kills HIV and blocks its oral transmission in humanized mouse

More than 15 percent of new HIV infections occur in children. Without treatment, only 65 percent of HIV-infected children will live until their first birthday, and fewer than half will make it to the age of two. Although breastfeeding is attributed to a significant number of these infections, most breastfed infants are not infected with HIV, despite prolonged and repeated exposure.

Immune cells in the gut may improve control of HIV growth

The findings of a new study in monkeys may help clarify why some people infected with HIV are better able to control the virus. They also may pinpoint a target for treatment during early HIV infection aimed at increasing the supply of certain immune cells in the gut, which the study shows could be an important factor in limiting HIV growth in cells throughout the body.

Revealed: Secret of HIV's natural born killers

Only about one person in 300 has the ability to control the human immunodeficiency virus (HIV) without drugs, using a strain of "killer" cells called cytotoxic T lymphocyte (CTL) cells, previous research has found.Taking that discovery further, scientists from the United States, Canada, Japan and Germany reported that the strain has molecules called receptors that are better able to identify HIV-infected white blood cells for attack.

International Symposium on HIV & Emerging Infectious Diseases (Open access abstracts)

The Abstracts of the International Symposium on HIV & Emerging Infectious Diseases held May 23-25 in Marseilles, France are available online. They are published on www.retrovirology.com as individual articles and a PDF file of 54 pages. You can go and have a look at them on the website of this top quality open access journal that have an impact factor of 5.24: http://www.retrovirology.com/supplements/9/S1

Research team uncovers mechanism behind drugs that cause altered immunity

(Medical Xpress) -- An Australian research team has opened the door to understanding why certain drugs cause a so called altered immunity response when offered as treatment for certain specific ailments. In their paper published in the journal Nature, the team explains how they’ve uncovered the mechanism that causes an HIV treatment drug to lead to hypersensitivity syndrome.