I thought this interesting since POTUS mentioned last night “A cure for HIV, AIDS. Some pretty interesting & freaky genetic research on this site

Science Newsfrom research organizations

How HIV infection may contribute to wide-ranging metabolic conditions

Date: July 25, 2019

Source: PLOS

Summary:

HIV-infected cells release vesicles that contain a viral protein called Nef, impairing cholesterol metabolism and triggering inflammation in uninfected bystander cells, according to a new study.

HIV-infected cells release vesicles that contain a viral protein called Nef, impairing cholesterol metabolism and triggering inflammation in uninfected bystander cells, according to a study published July 25 in the open-access journal PLOS Pathogens by Dmitri Sviridov of the Baker Heart and Diabetes Institute in Australia, and colleagues. The findings may explain how HIV infection causes a wide range of conditions that are associated with dysfunction in uninfected cells.

HIV infects only a limited repertoire of cells expressing HIV receptors. But HIV infection is also associated with conditions involving the dysfunction of cells that cannot be infected by HIV, such as hardening of the arteries, dementia, kidney impairment, and certain heart problems. These HIV-associated conditions persist even after successful application of antiretroviral therapy, when no virus is found in the blood. Many of these conditions involve impairments in cholesterol metabolism. In the new study, Sviridov and colleagues examined the mechanisms that may contribute to HIV-associated metabolic conditions.

The results showed that the HIV protein Nef is released from infected cells in vesicles that are then rapidly taken up by uninfected bystander white blood cells, impairing cholesterol metabolism in these cells. This impairment causes the formation of excessive lipid rafts – discrete lipid domains present in the external leaflet of the plasma membrane – and the re-localization of inflammatory receptors into rafts, triggering inflammation. The findings demonstrate how a single viral molecule released from infected cells into circulation may contribute to a range of pathogenic responses.

The authors add, "Our study points to a common mechanism of various co-morbidities of HIV infection. This opens a possibility to target this mechanism using drugs affecting cholesterol metabolism to treat several co-morbidities in people living with HIV."

https://www.sciencedaily.com/releases/2019/07/190725150946.htm

Science Newsfrom research organizations

Scientists pinpoint new mechanism that impacts HIV infection

Date: July 24, 2019

Source: Texas Biomedical Research Institute

Summary:

Scientists have published results of a study that pinpointed a long noncoding RNA molecule which influences a key receptor involved in HIV infection and progression of the disease. This newly-identified mechanism could open up a new avenue for control of HIV, the virus that causes AIDS.

The article was published in a recent edition of the journal Nature Immunology.

Most of the genome is made up of noncoding RNAs which do not directly translate into proteins. In fact, 97% of the human genome is non-protein coding. Dr. Kulkarni says that until the last decade or so, scientists thought many of these particular RNAs were "junk." Now, new research shows they play many roles. Recent developments in technology and genomics have made advances in knowledge in this area possible.

Dr. Kulkarni and her colleagues showed that a specific long noncoding RNA impacts the gene encoding the HIV co-receptor CCR5. Since CCR5 is critical for the HIV virus to enter the cell, a polymorphism associated with variation in expression of this long noncoding RNA impact the infection's outcome. Genomic DNA from various groups including Hispanics, African Americans and Japanese showed that this association is present across many ethnicities. This consistency of this association across populations speak to a single functional mechanism explaining this association.

Nature Immunology also featured a commentary about the study called "A SNP of lncRNA gives HIV-1 a boost" to further underscore the importance of this study to the field. In the article, Sanath Kumar Janaka and David T. Evans write "this study provides new insight into how polymorphisms in regulatory elements may explain genetic variation in pathogenesis." They go on to call Dr. Kulkarni's discovery a "fascinating and intricate mechanism."

"Their comments are encouraging and impel us to explore further," Dr. Kulkarni said."

HIV is still a major public health burden. More than a million people are living with HIV in the U.S. alone. More than 50,000 new cases are reported each year.

https://www.sciencedaily.com/releases/2019/07/190724112751.htm

New CRISPR platform expands RNA editing capabilities

The new system, dubbed RESCUE, allows RNA edits to be made that were not previously possible

Date: July 11, 2019

Source: Massachusetts Institute of Technology

Summary:

The new system, dubbed RESCUE, allows RNA edits to be made that were not previously possible.

https://www.sciencedaily.com/releases/2019/07/190711141338.htm

McGovern Institute Investigator and Broad Institute of MIT and Harvard core member Feng Zhang and his team have now developed one such strategy, called RESCUE (RNA Editing for Specific C to U Exchange), described in the journal Science.

Zhang and his team, including first co-authors Omar Abudayyeh and Jonathan Gootenberg (both now McGovern fellows), made use of a deactivated Cas13 to guide RESCUE to targeted cytosine bases on RNA transcripts, and used a novel, evolved, programmable enzyme to convert unwanted cytosine into uridine – thereby directing a change in the RNA instructions. RESCUE builds on REPAIR, a technology developed by Zhang's team that changes adenine bases into inosine in RNA.

RESCUE significantly expands the landscape that CRISPR tools can target to include modifiable positions in proteins, such as phosphorylation sites. Such sites act as on/off switches for protein activity and are notably found in signaling molecules and cancer-linked pathways.

"To treat the diversity of genetic changes that cause disease, we need an array of precise technologies to choose from. By developing this new enzyme and combining it with the programmability and precision of CRISPR, we were able to fill a critical gap in the toolbox," says Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT. Zhang has appointments in MIT's departments of Brain and Cognitive Sciences and Biological Engineering.

Expanding the reach of RNA editing to new targets

The previously developed REPAIR platform used the RNA-targeting CRISPR/Cas13 to direct the active domain of an RNA editor, ADAR2, to specific RNA transcripts where it could convert the nucleotide base adenine to inosine, or letters A to I. Zhang and colleagues took the REPAIR fusion and evolved it in the lab until it could change cytosine to uridine, or C to U.

RESCUE can be guided to any RNA of choice, then perform a C-to-U edit through the evolved ADAR2 component of the platform. The team took the new platform into human cells, showing that they could target natural RNAs in the cell, as well as 24 clinically relevant mutations in synthetic RNAs. They then further optimized RESCUE to reduce off-target editing, while minimally disrupting on-target editing.

New targets in sight

Expanded targeting by RESCUE means that sites regulating activity and function of many proteins through post-translational modifications, such as phosphorylation, glycosylation, and methylation, can now be more readily targeted for editing.