Meet Bill Gates

Genetic Dark Matter:
Return of the Goddess

Every living thing is connected via webs of genetic and epigenetic relationships.

mRNAs function as cross-kingdom master regulators of the fellowship of the biosphere.

Produced by bacteria, fungi, plants, and animals, mRNAs are capable of surviving digestive and assimilative processes intact, entering the tissues of organisms, affecting the expression of a wide range of genes.

Immunopathogenesis of HIV infection

COVID-19: genetic network analysis

"The viral network we have detailed is a snapshot of the early stages of an epidemic,
before the evolutionary paths of COVID-19 become obscured by vast numbers of mutations.
It's like catching an incipient supernova in the act." - Peter Forster

Vehicles of intercellular communication

Viral surface glycoproteins, gp120 and gp41, as potential drug targets against HIV-1

Chimpanzees Immunized with Human Immunodeficiency Virus Envelope Glycoprotein

Simian Virus 40 (SV40):
A Cancer Causing Monkey Virus from FDA-Approved Vaccines

Scientist who spiked rabbit blood to fake HIV Vaccine Results Gets Rare Prison Sentence

Bill Gates donates $10m to Australian trial of immune-boosting vaccine

Combinatorial CRISPR-Cas9 and RNA Interference Attack
on HIV-1 DNA and RNA Can Lead to Cross-Resistance

"At the beginning of an article on the human immunodeficiency virus, (HIV, the putative causal agent of AIDS that he and others isolated), Dr. Robert C. Gallo observes without comment that epidemiologists had named the new disease "acquired immune deficiency syndrome."

By attributing the power to name the disorder to them, Dr. Gallo shows us how prominent a part epidemiology has played in defining and ordering this "medical mystery."

I examine the role of epidemiology in characterizing HIV infection.

Faced with a new disease of unknown origin, epidemiologists and their collaborators constructed, over time, hypothetical models to explain the disorder in order to contain it.

Prior to the isolation of a putative causal agent, HIV, epidemiologists played a central role in defining the new syndrome, first developing a "life-style" model and, later, a model based on hepatitis B.

Supplanted by virologists and other "bench" scientists working in laboratories, epidemiologists have continued to define important dimensions of the disorder and raise disquieting questions.

Epidemiologists were concerned with defining the natural history of HIV infection, the extent to which it spread within population groups, factors affecting the spread rates of the virus.

Epidemiology, unlike virology, has a strong social dimension in that it explicitly incorporates perceptions of a population's social relations, behavioral patterns, and experiences into its explanations of disease." - Gerald M. Oppenheimer

In the Eye of the Storm: The Epidemiological Construction of AIDS

HIV envelopolype peptides

Beneficial Effects of Cannabis on Blood Brain Barrier Function in HIV

Use of antagonists of the interaction between HIV GP120 and A4B7 integrin

Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein

Select gp120 V2 domain specific antibodies derived from HIV
and SIV infection and vaccination inhibit gp120 binding to α4ß7

Role for mRNAs as inter-species
mediators of epigenetic information

mRNAs are short non-coding RNA molecules involved in the posttranscriptional epigenetic regulation of gene expression.

Recent data show that mRNAs can be found in body fluids, and these mRNAs might enter cells giving rise to a hormone like way of action.

mRNAs released in body fluids might affect other individuals, and there are some data of potential cross-species action of mRNAs.

mRNAs traverse the gastrointestinal tract.

mRNAs wander via the food-chain.

Master regulatory mRNAs may influence gene expression.

mRNA genes, located in the non-protein coding "dark matter" of the genome, may facilitate interindividual and cross-species epigenetic communication via information transfer by coded gene products.

HIV-infected cells persist only for a day or two.
HTLV is thought to replicate by promoting proliferation of infected cells.
"Assume about 10 years between HIV infection and diagnosis of AIDS." - ASF

Retroviral integration and human gene therapy

HIV in gene therapy to fix 'bubble boy' disease

The simian foamy virus (SFV), a spumavirus, has been co-speciated with Old World primates for about 30 million years, making them the oldest known vertebrate RNA (ribonucleic acid) or retrovirus.

late 1950's SV40, a retrovirus, is identified in the injected form of the polio vaccine.

This is believed to be due to kidney cells from infected monkeys being used to amplify the vaccine virus during production.

Both the Sabin vaccine (oral, live virus) and the Salk vaccine (injectable, killed virus) are affected; the technique used to inactivate the polio virus in the Salk vaccine, by means of formaldehyde, does not reliably dissolve SV40.

When two or more vaccines are mixed together in the same formulation, the two vaccines can interfere.

This most frequently occurs with 'live' attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response of the other components.

This phenomenon is first noted in the trivalent Sabin polio vaccine, where the amount of serotype 2 virus in the vaccine has to be reduced to stop it from interfering with the "take" of the serotype 1 and 3 in the vaccine.

SIVagm is a lentivirus also a retrovirus.

The genome consists of two strands, a longer negative-sense strand and a shorter and positive-sense strand of variable length.

In the virion these strands are arranged such that the two ends of the long strand meet but are not covalently bonded together.

The virus binds to receptors allowing viral particles to enter the cytoplasm.

This is then translocated to the nucleus, where the partially double stranded DNA is 'repaired' by the viral polymerase to form a complete circular dsDNA genome (called covalently-closed-circular DNA or cccDNA).

The genome then undergoes transcription by the host cell RNA polymerase and the pregenomicRNA (pgRNA) is sent out of the nucleus.

A polymerase is an enzyme that synthesizes long chains of polymers.

(DNA polymerase and RNA polymerase are used to assemble DNA and RNA molecules, respectively, by copying a DNA template strand using base-pairing interactions or RNA by half ladder replication.)

pgRNA penetrates an assembled viral capsid containing the viral polymerase.

Inside this capsid the genome is converted from RNA to pdsDNA through activity of the polymerase as an RNA-dependent-DNA-polymerase and subsequently as an RNAse to eliminate the pgRNA transcript.

New virions either leave the cell to infect others or are immediately dismantled so the new viral genomes can enter the nucleus and magnify the infection.

The virions that leave the cell egress through budding.

This is a deoxyribonucleic acid virus.

1958 Denis Parsons Burkitt describes a β lymphocyte cancer of the lymphatic system found in the germinal center.

Michael Anthony Epstein, a British pathologist and academic, proposes Burkitt's lymphoma is a cancer caused by a virus.

Epstein changes his research focus to a viral origin of Burkitt's lymphoma.

After more than two years of working with tumour cells from Burkitt's patients Epstein claims to have isolated the the Epstein–Barr virus.

Epstein-Barr virus, also known as human herpesvirus 4, is a member of the herpes virus family. It is one of the most common human virus.

Epstein–Barr infection is found in most patients with Burkitt lymphoma.

Burkitt lymphoma strikes 30-40% of individuals with HIV-induced AIDS.

Mononucleosis is thought to spread most commonly through bodily fluids.

Adolescents were told if you kissed you would get the Kissing disease.

Mono Virus Discovery

Infectious Mononucleosis (Mono) | Epstein-Barr Virus

Exaggerated Villainy of the Epstein-Barr Virus

Neurological Symptoms in Multiple Sclerosis

Morphologic Features of Epstein-Barr Virus Infection in the GI Tract

Relationship between Epstein-Barr and Cell Membrane

"Blastoid cell cultures derived from leukocytes of patients in the acute stage of infectious mononucleosis (IM) and harboring Epstein-Barr (EB) virus in at least 1% of the cells were found to possess antigens in their membranes which presently are indistinguishable from those detected in Burkitt's lymphoma (BL) cells by the techniques employed." - Rockefeller University Press

Peptides derived from cellular proteins are continuously exposed at the cell surface.

The role of exosomal transport of viral agents

Exosomes in Human Immunodeficiency Virus Type I Pathogenesis

Another HIV vaccine strategy fails in large-scale study

Antibody persistence and T lymphocyte balance: HIV vaccine development

late 1960s Observers "isolate" and then inoculate with the MS-2 strain of hepatitis B virus.

Hepatitis virus replicates through an RNA intermediate form by reverse transcription, and in this respect they are similar to retrovirus.

Hepatitis B virus belongs to the Hepadnavirus family.

Hepadnavirus have very small genomes of partially double-stranded, partially single stranded circular DNA.

Was There an AIDS Contract?

What Really Caused The AIDS Epidemic?

early 1970s African rhesus monkeys are used in the manufacture of the hepatitis B vaccine.

Human hepatitis B virus cultured in vivo in rhesus monkeys are returned to humans whose infected blood serum is then pooled to develop four different strains of experimental hepatitis B vaccine.

Experimental vaccine clinical trial in New York City and central Africa.

Hepatitis B vaccine recipients worldwide, including gay men in New York, and Black Africans in Central Africa, are exposed to simian virus including SV40, SIVagm, and perhaps others.

A generally neglected evolutionary route of SIVagm to HIV-1 zoonosis sequentially involves:

a) human incubation for more than a decade of polio vaccine contaminants and recombinants including SV40, SFR, and possibly SIVagm;

b) the pooling of infected blood serum donated by hundreds of gay American and Black African hepatitis B vaccine recipients who had subsequently received injections with cultured strains of hepatitis B virus;

c) the biohazardous laboratory conditions and viral containment problems reported by the hepatitis B vaccine investigators and their affiliates;

This series of events provides the best explanation for an early to mid-1970s "punctuated origin event" most precisely fitting etiological determinations of the HIV-1/AIDS pandemic.

There is evidence demonstrating that the schizophrenia associated retrovirus (SZRV) is an autoimmune disorder causing retrovirus in the Type-D family of retrovirus, e.g., SRV-1 (simian retrovirus type 1), SRV-2 (simian retrovirus type 2), M7 (baboon endogenous retrovirus), SMRV-H (squirrel monkey retrovirus), HTLV (human T lymphocyte leukaemia virus) and distantly-related to HIV (human immunodeficiency virus).

1972 World Health Organization Bulletin No. 47 refers to creation of an immune virus and suggests that a useful way to study the effects would be "to put it into a vaccination program and observe the results".

Curiously the spread of HIV infection in Central Africa coincides precisely with an intense smallpox vaccination campaign.

Information on Central African countries infected with HIV matches WHO figures indicating the number of people vaccinated in these areas.

Government Documents Locked Up for 30 Years Prove This Vaccine Unsafe

mRNA Platform

Imperfect vaccines and herd immunity to HIV

Development and Evaluation of a Vaccine for HIV Infection

Another HIV Vaccine Fails a Trial, Disappointing Observers

Antibody persistence and T lymphocyte balance:
Two key factors confronting HIV vaccine development

HIV vaccine development presents novel challenges on multiple levels.

The chief challenge is HIV human retrovirus replicates by irreversibly inserting its genes into the host genome.

HIV infection is established permanently in a matter of days or even hours, and it cannot be cleared by primary or anamnestic responses.

In addition to integrating into the host genome, HIV replicates in CD4+ T cells that are key players in protective immunity.

These features suggest a different path to a HIV vaccine from traditional design that led to successful vaccines against other infectious agents.

Inability to yield an HIV vaccine became abundantly clear in six large HIV vaccine trials, where efficacy was not observed.

Strikingly, vaccination increased the risk of infection in two of these studies that selectively targeted T lymphocyte immunity, providing a stark contrast between the development of conventional and HIV vaccines.

Cannabis in HIV-associated sensory neuropathy: a randomized placebo-controlled trial

Cannabinoid inhibits HIV-1 adhesion of monocyte cells to extracellular matrix proteins

Pre-existing and de novo humoral immunity to SARS-CoV-2 in humans

SARS-CoV-2 T lymphocyte epitopes define heterologous and COVID-19-induced T lymphocyte recognition

SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS

1983   French team at the Pasteur Institute in Paris led by Luc Montagnier, publish a paper in Science describing a retrovirus, LAV (lymphadenopathy associated virus), isolated from a patient at risk for AIDS.

LAV affects the way the immune system works.

May 6, 1983   "The disease was first believed to be confined to a particular epidemiologically defined segment of the population.

Earlier hypotheses suggested there was something within the lifestyle of male homosexuals that predisposed them to this syndrome.

Theories put forth suggesting drugs such as amyl nitrite, antigenic overload, and medications taken for multiple infections affecting male homosexuals." - Anthony S. Fauci, National Institutes of Health; Acquired Immune Deficiency Syndrome: Ever-Broadening Clinical Spectrum

May 4, 1984   Robert Gallo, an observer at the National Cancer Institute where he has worked for 30 years mainly as head of the Laboratory of Tumor Cell Biology, and collaborators publish a series of four papers in Science demonstrating that a retrovirus they claim to have isolated is the cause of AIDS, HTLV-III, related to the leukaemia virus of Gallo's earlier work.

Method of continuous production of retrovirus (HTLV-III)

1987 Immune system compromise brings AIDS companion cancers include Kaposi sarcoma, aggressive βlymphocyte non-Hodgkin lymphoma and cervical cancer.

Other cancers linked to immune compromised by HIV/AIDS are head and neck, anal, lung, testicle, skin, and liver cancers as well as Hodgkin lymphoma.

Out of court settlement between the National Institutes of Health (NIH)and Pasteur Institute in Paris.

Bipolar Barney

Cannabis Enhances Bipolar Patients' Neurocognitive Performance

Do 5 Million Americans Really Have Bipolar Disorder?

Immune activation by casein dietary antigens

Cognitive and clinical outcomes associated with
cannabis use in patients with bipolar I disorder

Bipolar disorder and the endocannabinoid system

Results from our analysis suggest that subjects with bipolar disorder and history of cannabis use disorders demonstrate significantly better neurocognitive performance, particularly on measures of attention, processing speed, and working memory.

These findings are consistent with a previous study that demonstrated that bipolar subjects with history of cannabis use had superior verbal fluency performance as compared to bipolar patients without a history of cannabis use (Ringen et al., 2010).

Similar results have also been found in schizophrenia in several studies (Rabin et al., 2011).

These data could be interpreted to suggest that cannabis use may have a beneficial effect on cognitive functioning in patients with severe psychiatric disorders.

1988 Amalgamated HepB vaccine introduced.

1991 Amalgamated HepB vaccine mandated by Centers for Disease Control in 44 US states for initial use in infants as young as two months.

New York Times, Mar 17th, "US Vaccine Plan Uses Welfare Offices": Feds are considered denying nutritional benefits to families who refuse vaccinations.

The begins the process of mandating Hepatitis B vaccinations for all infants in the United States. Many infants receive multiple doses from birth.

Following years of controversy surrounding the out of court settlement between the National Institutes of Health and the Pasteur Institute, Gallo admits the virus he claimed to have discovered in 1984 is in reality a virus sent to him from France the year before, putting an end to a six-year effort by Gallo and his employer, the National Institutes of Health, to claim the AIDS virus as an independent discovery.

Hepatitis B vaccination of male neonates and autism diagnosis

Court Admits Hepatitis B Vaccine Caused Fatal Autoimmune Disorder

Connective Tissue Disease Following Hepatitis B Vaccination

1993 "This paper shows how to equate different aspects of imperfection in a prophylactic vaccine in terms of impact upon levels of herd immunity, and hence upon the vaccine coverage required for eradication.

Such comparisons reveal that an otherwise perfect vaccine that gives protection which wanes with a half-life of 10 years is only as good as a vaccine that works in 30% of people giving them complete, lifelong protection." - Imperfect vaccines and herd immunity to HIV

1994   20,000 American children and adolescents are diagnosed with bipolar disorder.

1995 Gallo with his colleagues Paolo Lusso and Fiorenza Cocchi publish their discovery that chemokines, a class of naturally occurring compounds, are potent and specific HIV inhibitors.

This discovery is heralded by Science magazine as one of the top scientific breakthroughs of the year.

The role chemokines play in controlling the progression of HIV infection influences thinking on how AIDS works against the human immune system.

1996   "Despite unanimous literature of double-blind studies indicating antiDepressant are no more effective than placebo in treating depression in children and adolescents, such medications continue to be in wide use." - Rhoda L. Fisher and Seymour Fisher, "antiDepressant for Children," The Journal of Nervous and Mental Diseases (1996, v.184, no.2)

Gallo, Robert R. Redfield and William A. Blattner, found the Institute of Human Virology.

Autoimmune adverse events following hepatitis B immunization

Chronic fatigue/fibromyalgia follow immunization with hepatitis B vaccine:
'autoimmune (auto-inflammatory) syndrome induced by adjuvants' (ASIA)

2003   800,000 children and adolescents are diagnosed with bipolar disorder - exponentially increasing 40 times levels 9 years earlier.

2005   Dr. Frederick K. Goodwin warns that children with bipolar disorder who were left untreated could suffer brain damage.

Dr. Frederick K. Goodwin, a former director of the National Institute of Mental Health, and host of the popular public radio program "The Infinite Mind," produced by Lichtenstein Creative Media, earns at least $1.3 million from 2000 to 2007 giving marketing lectures for drugmakers.

"Boys, behaving aggressively exhibiting irritable behavior become compliant when given mood stabilizers and parents are relieved of the stigma of poor parenting as bipolar disorder is thought to be an inherited trait."

Modern treatments - mood stabilizers in particular - have been proven both safe and effective in bipolar children." - Frederick K. Goodwin

"I call it the juvenile bipolar juggernaut. The diagnoses has been broadened considerably and I think that's a big problem." - Joseph Woolston, Yale

"The risk of violence on these drugs has been known for 50 years.

Giving these drugs to healthy volunteers can cause them to become violent.

The data has been out there in warnings in many countries for years.

There is no doctor who can say they have been unaware of this issue.

If there are, they are simply not professional." - David Healy

2007 Gallo and his team are awarded a $15 million grant from the Gates Foundation for research into a preventive vaccine for HIV/AIDS.

2010 Abstract:

"To develop safer and more effective vectors for gene therapy of X-linked severe combined immunodeficiency (SCID-X1), we have evaluated new self-inactivating lentiviral vectors based on the HIV virus.

The CL20i4-hγc-Revgen vector contains the entire human common γ chain (γc) genomic sequence driven by the γc promoter.

The CL20i4-EF1α -hγcOPT vector uses a promoter fragment from the eukaryotic elongation factor alpha (EF1α ) gene to express a codon-optimized human γc cDNA.

Both vectors contain a 400-bp insulator fragment from the chicken ß-globin locus within the self-inactivating long-terminal repeat.

Transduction of bone marrow cells using either of these vectors restored T, B, and natural killer lymphocyte development and function in a mouse SCID-X1 transplantation model.

Transduction of human CD34+ bone marrow cells from SCID-X1 patients with either vector restored T lymphocyte development in an in vitro assay.

In safety studies using a Jurkat LMO2 activation assay, only the CL20i4-EF1α-hγcOPT vector lacked the ability to transactivate LMO2 protein expression, whereas the CL20i4-hγc-Revgen vector significantly activated LMO2 protein expression.

In addition, the CL20i4-EF1α-hγcOPT vector has not caused any tumors in transfected mice.

We conclude that the CL20i4-EF1a-hγcOPT vector may be suitable for testing in a clinical trial based on these preclinical demonstrations of efficacy and safety.

A self-inactivating lentiviral vector for SCID-X1 gene therapy

2011 Gallo and his team received $23.4 million from a consortium of funding sources to support the next phase of research into the Institute of Human Virology's (IHV) promising HIV/AIDS preventive vaccine candidate.

The IHV vaccine program grants included $16.8 million from the Gates Foundation, $2.2 million from the U.S. Army's Military HIV Research Program (MHRP), and other research funding from a variety of sources including the National Institutes of Health.

2019 Abstract:

Gene correction in human long-term hematopoietic stem cells (LT-HSCs) could be an effective therapy for monogenic diseases of the blood and immune system.

Here we describe an approach for X-linked sSevere cCombined iImmunodeficiency (SCID-X1) using targeted integration of a cDNA into the endogenous start codon to functionally correct disease-causing mutations throughout the gene.

Using a CRISPR-Cas9/AAV6 based strategy, we achieve up to 20% targeted integration frequencies in LT-HSCs.

As measures of the lack of toxicity we observe no evidence of abnormal hematopoiesis following transplantation and no evidence of off-target mutations using a high-fidelity Cas9 as a ribonucleoprotein complex.

We achieve high levels of targeting frequencies (median 45%) in CD34+ HSPCs from six SCID-X1 patients and demonstrate rescue of lymphopoietic defect in a patient derived HSPC population in vitro and in vivo.

In sum, our study provides specificity, toxicity and efficacy data supportive of clinical development of genome editing to treat SCID-Xl.

Gene correction for SCID-X1 in long-term hematopoietic stem cells

Chronic administration of Δ9tetrahydrocannabinol induces intestinal anti-inflammatory mRNA expression

Gastrointestinal (GI) tract disease/inflammation is a hallmark of HIV/SIV infection.

Recreational and medical use of cannabis among human immunodeficiency virus (HIV)-infected individuals has increased in recent years.

In simian immunodeficiency virus (SIV)-infected macaques, chronic administration of Δ9tetrahydrocannabinol (Δ9THC) inhibited viral replication and intestinal inflammation and slowed disease progression.

Persistent gastrointestinal inflammation has been proposed to facilitate microbial translocation and systemic immune activation and promote disease progression.
Cannabinoids including Δ9THC attenuated intestinal inflammation in mouse colitis models and SIV-infected rhesus macaques.

To determine if the anti-inflammatory effects of Δ9THC involved differential mRNA (mRNA) modulation, we profiled mRNA expression at 14, 30, and 60 days postinfection (days p.i.) in the intestine of uninfected macaques receiving Δ9THC (n=3) and SIV-infected macaques administered either vehicle (VEH/SIV; n=4) or THC (THC/SIV; n=4).

Chronic Δ9THC administration to uninfected macaques significantly and positively modulated intestinal mRNA expression by increasing the total number of differentially expressed mRNAs from 14 to 60 days p.i. At 60 days p.i., ~28% of mRNAs showed decreased expression in the VEH/SIV group compared to none showing decrease in the THC/SIV group.

Furthermore, compared to the VEH/SIV group, THC selectively upregulated the expression of miR-10a, miR-24, miR-99b, miR-145, miR-149, and miR-187, previously been shown to target proinflammatory molecules.

NOX4, a potent reactive oxygen species generator, was confirmed as a direct miR-99b target. A significant increase in NOX4+ crypt epithelial cells was detected in VEH/SIV macaques compared to the THC/SIV group.

We speculate that miR-99b-mediated NOX4 downregulation may protect the intestinal epithelium from oxidative stress-induced damage.

These results support a role for differential mRNA induction in THC-mediated suppression of intestinal inflammation.

Whether similar mRNA modulation occurs in other tissues requires further investigation.

Previously, we showed that chronic treatment of SIV-infected macaques with Δ9tetrahydrocannabinol (Δ9THC) increased survival and decreased viral replication and infection-induced gastrointestinal inflammation.

Here, we show that chronic THC administration to SIV-infected macaques induced an anti-inflammatory mRNA expression profile in the intestine at 60 days p.i.

These included several mRNAs bioinformatically predicted to directly target CXCL12, a chemokine known to regulate lymphocyte and macrophage trafficking into the intestine.

Specifically, mR-99b was significantly upregulated in THC-treated SIV-infected macaques and confirmed to directly target NADPH oxidase 4 (NOX4), a reactive oxygen species generator known to damage intestinal epithelial cells.

Elevated mR-99b expression was associated with a significantly decreased number of NOX4+ epithelial cells in the intestines of THC-treated SIV-infected macaques.

Overall, our results show that selective upregulation of anti-inflammatory mRNA expression contributes to THC-mediated suppression of gastrointestinal inflammation and maintenance of intestinal homeostasis.

Δ9Tetrahydrocannabinol Promotes Neuroimmune-Modulatory mRNA
Profile in Striatum of Simian Immunodeficiency Virus (SIV)

Cannabinoids inhibit migration of microglial-like cells to the HIV protein Tat

Marijuana Smoking Does Not Accelerate Progression of Liver Disease in HIV–Hepatitis C Coinfection

chemical warfare

unique library index

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