Genet ically Marked
By Kathleen M. Urquhart
Mechanism of m RNA Transport in t he Nucleus
?We found that the rate of Messenger RNP (mRNA-protein) diffusion is so fast that mRNP
complexes are dispersed throughout the nucleus soon after their synthesis and well
before the onset of significant export into the cytoplasm.?
?Using molecular beacons to track single mRNA molecules in living cells, we have
characterized the diffusion of mRNP (mRNA-protein) complexes in the nucleus. The
mRNP complexes move freely by Brownian diffusion at a rate that assures their
dispersion throughout the nucleus before they exit into the cytoplasm, even when the
transcription site is located near the nuclear periphery.?
Diana Y. Vargas, Arjun Raj, Salvatore A. E. Marras, Fred Russell Kramer, Sanjay Tyagi
Proceedings of the National Academy of Sciences Nov 2005, 102 (47) 17008-17013;
Please read: https://www.pnas.org/content/102/47/17008.long
Abst ract -Recent Advances in t he Molecular Beacon Technology for Live-Cell
Single-Molecule Im aging
Nucleic acids, aside from being best known as the carrier of genet ic inform at ion, are
versatile biomaterials for constructing nanoscopic devices for biointerfacing, owing to their
unique properties such as specific base pairing and predictable structure. For live-cell analysis
of native RNA transcripts, the most widely used nucleic acid-based nanodevice has been the
molecular beacon (MB), a class of stem-loop-forming probes that is activated to fluoresce
upon hybridization with target RNA.
Mao S, Ying Y, Wu R, Chen AK. Recent Advances in t he Molecular Beacon Technology for
Live-Cell Single-Molecule Im aging. iScience. 2020 Nov 13;23 (12):101801. doi:
10.1016/j.isci.2020.101801. PMID: 33299972; PMCID: PMC7702005.
Wiki: Molecular beacons, or m olecular beacon probes, are oligonucleotide hybridization
probes that can report the presence of specific nucleic acids in homogenous solutions.
Wiki: ( mRNA-protein) Messenger RNP: Messenger RNP (m essenger ribonucleoprot ein) is
m RNA wit h bound prot eins. mRNA does not exist “naked”i n vivo but is always bound by
various proteins while being synthesized, spliced, exported, and translated in the cytoplasm.
Wiki: RNA Vaccine – An RNA vaccine or m RNA (m essenger RNA) vaccine is a type of vaccine
that uses a copy of a natural chemical called messenger RNA (mRNA) to produce an immune
response. The vaccine transfects molecules of synt het ic RNA into immunity cells.
mRNA vaccines introduce a short-lived  synt het ically creat ed fragm ent of t he RNA
sequence of a virus into the vaccinated individual.
RNA Biol. 2016 Sep; 13(9): 760?765.
Published online 2016 Jun 28. doi: 10.1080/15476286.2016.1203504
m RNA m odificat ions: Dynam ic regulat ors of gene expression?
Thomas Philipp Hoernes,Alexander Hüttenhofer, and Matthias David Erlacher
The expression of a gene is a tightly regulated process and is exerted by a myriad of different
mechanisms. Recently, RNA modifications located in coding sequences of mRNAs, have been
identified as potential regulators of gene expression. N6-methyladenosine (m6A),
5-methylcytosine (m5C), pseudouridine (? ) and N1-methyladenosine (m1A) have been found
within open reading frames of mRNAs. The presence of these mRNA modifications has been
implicated to modulate the fate of an mRNA, ranging from maturation to its translation and
even degradation. However, many aspects concerning the biological functions of mRNA
modifications remain elusive. Recently, systematic in vitro studies allowed a first glimpse of
the direct interplay of mRNA modifications and the efficiency and fidelity of ribosomal
translation. It thereby became evident that the effects of mRNA modifications were,
astonishingly versatile, depending on the type, position or sequence context. The
incorporation of a single modification could either prematurely terminate protein synthesis,
reduce the peptide yield, or alter the amino acid sequence identity. These results implicate
that mRNA modifications are a powerful m echanism t o post -t ranscript ionally regulat e
Post-transcriptional mRNA modifications might even possess the potential to expand the
diversity of proteins through recoding. Therefore, it is of utmost importance to elucidate all
mechanisms behind. mRNA modifications not only affect translation, but can also act as
m arkers to provide landing platforms for proteins 61,62,85,86 or stimulate other regulatory
processes like mRNA degradation 60 or localization. 87 Their role as m arkers is reminiscent of
the regulation of gene expression through epigenetic DNA and histone modifications. In line
with that, not single m odificat ions but a com binat ion t hereof m ight collect ively m ediat e
biological funct ions.
WIKI: Viral Vect ors: Viral vect ors [edit ]
Main article: Viral vector
Viral vectors are generally genetically engineered viruses carrying modified viral DNA or RNA
that has been rendered noninfectious, but still contain viral promoters and also the transgene,
thus allowing for translation of the transgene through a viral promoter. However, because viral
vectors frequently are lacking infectious sequences, they require helper viruses or packaging
lines for large-scale transfection. Viral vectors are often designed for permanent incorporation
of the insert into the host genome, and thus leave distinct genetic markers in the host genome
after incorporating the transgene. For example, retroviruses leave a characteristic retroviral
integration pattern after insertion that is detectable and indicates that the viral vector has
incorporated into the host genome.
Anthony and I are frequently asked if this vaccine is ?The Mark of the Beast?. If taken, does it
change your DNA? Is your name removed from the ?Lamb?s Book of Life? I?d like to take this
opportunity to share with you information that we have that, to us, makes these points
unmistakably clear. It addresses the biological as well as our faith-based system of belief.
Acknowledging this vaccination agenda as the beginning or ?roll-out? of the Mark of the Beast
System (MOBS) will only resonate with those who are true children of God and are in tune/close
communication with his Holy Spirit. Sadly, we are discovering that many Christian pastors are
not sharing this vital information with their congregations. They will be accountable to God for
withholding such soul-saving knowledge.
The word ?mark? has many meanings. It can mean dot, spot, blemish, or smear. It can mean
sign, token, symbol, or badge. It can mean a level,stage, or degree. It can mean grade, score,
or percentage. It can mean target, goal, or objective. It can mean to certify, name, initial, label,
seal, or signature. It can mean observe, recognize, acknowledge, or scrutinize. It can mean
separate, characterize, distinguish, or identify. It can mean assess, evaluate, or appraise (as in a
grade). It can mean heed, listen to, or take notice of.
Ephesians 5:27,KJV: “That he might present it to himself a glorious
church, not having spot, or wrinkle, or any such thing; but that it should
be holy and without blemish.”
With respect to ?Mark of the Beast? as worded in Revelation, it takes on the form of a
charagm a (in the Greek ?charax? meaning a pointed stake or palisade), an engraving (tool) or
sharp pointed object, stamp, or imprint/impression. It is the badge of the followers of
Antichrist, engraved/stamped/impressed on the right hand or forehead. (See Revelation: 13:16
& 17; 14:9 & 11; 16:2; 19:20; and 20:4).
? 5480. charagm a?
St rong’s Concordance
charagm a: a st am p, im press
Original Word:???????, ????, ??
Part of Speech:Noun, Neuter
Translit erat ion:charagma
Phonet ic Spelling:(khar’-ag-mah)
Definit ion:a stamp, impress
Usage:sculpture; engraving, a stamp, sign.
Ephesians 5:27,KJV: “That he might present it to himself a glorious
church, not having spot, or wrinkle, or any such thing; but that it should
be holy and without blemish.”
We have maintained, based on science, biology, technology, and study of scripture, that this
inoculation delivers into the human body an ?operating system? encompassing all of the
disciplines mentioned. See Moderna?s own mRNA science and technology platform and
professed ?Operating System?
mRNA WILL impact the human genome/body leaving its ?mark? within our genetic code.
Believing that the human body is the temple of God?s Holy Spirit (1 Cor. 6:19), we conclude
that this is the ?abomination that causes desolation? spoken of in Matthew 24:15 & 16 and in
Daniel Chapter 8.
This scientific/biological/technological ?vector? will deliver, disrupt, and permanently alter our
divinely created and unique designed genome. It will modify the entire molecular structure
of the human body from one thoughtfully and purposefully created by God to a yet-unknown
entity that Satan, with the help of science and technology, fatally manipulates. This mRNA
vaccine has never been used in human trials.
Wiki: The vect or itself is generally a DNA sequence that consists of an insert (transgene) and
a larger sequence that serves as the “backbone” of the vect or. The purpose of a vect or
which transfers genetic information to another cell is typically to isolate, multiply, or express
the insert in the target cell.
Rolled out much like a new software program, this first round of mRNA administration (We
will call it Distribution 1.0) will begin with an ultra cold mRNA fabrication delivered by way of a
syringe and hypodermic needle. In version 2.0, the look, feel, and ease of dispensing the
vaccine will change dramatically allowing for a self-administered microneedle array patch
that can be mailed to your door. It will come front-loaded with not only a new and improved
mRNA Covid cocktail, but will also house bio-sensing quantum dots, a bioluminescent ?tattoo?
utilizing an oxidative enzyme called Luciferase. This biological tattoo/CHARAGMA is needed
in order to mark, track, and identify those who have taken the vaccine. Highly sensitive
scanners from a mobile phone or stationary tracking system can read the quantum dot
tattoo that, though not visible to the human eye, is under near-infrared light.
The ?patch? will be billed as so simple that child could apply it. Simply unseal, press, and hold
for a few minutes. The keenly (coincidentally??) designed ?snake fang?inspired st am ping
pat ch? (This is the actual medical term), See:
ht t ps://st m .sciencem ag.org/cont ent /11/503/eaaw3329?int cm p=t rendm d-st m
will painlessly deliver a state-of-the-art operating system into your body that will connect you
to the technological ?beast? system. There will then be the ?seamless? transition into the
block chain system (Internet of Things) whereby all of your personal financial, educational,
medical, social, and professional information will be conveniently and ?confidentially? housed
in a cloud. Congratulations! You and your computer have now become ONE in the sentient
Does any of this sound familiar? It should. Satan does and says nothing original or unique.
Jesus st at ed FIRST in John 14:20:
?In t hat day you will know t hat I am in My Fat her, and you are in Me, and I in you.?
Then again in John 17:23:
?I in t hem , and t hou in m e, t hat t hey m ay be m ade perfect in one; and t hat t he world
m ay know t hat t hou hast sent m e, and hast loved t hem , as t hou hast loved m e.?
This mark/stamp/sign/impression/charagma is revealed in the many definitions stated
earlier about the word ?mark.? It is multi-faceted. It can be a ?dot? as applied today in
?quantum dots? which are used in research and labeling of biological material (in vitro and in
vivo). Quantum dots, crystals of a fluorescent semiconductor material with a diameter of as
few as 10 to100 atoms (2-10mm), can be inserted into cells and attach to proteins to
identify/label/track individual biomolecules due to their very narrow fluorescence spectra,
brightness and resistance to photobleaching. (Definition from Nature.com). According to
Samsung, and technologically speaking, ?A Quantum Dot is a human-made nanoparticle that
has semiconductor properties.?
Back to Distribution 1.0 ? in this beta test, people who have agreed to take the inoculation
will be issued a form of proof of vaccination. Some sort of physical pass, paper, or digital
record will certify their health compliance and declare them ?safe? to enter back into society.
In Distribution 2.0, the ?MNA? upgrade (Microneedle Array), brings with it technological
capabilities that will render paper prehistoric. Now the person carries around in their bodies
all of their ?records? to be scanned and maintained in ?the cloud? instantly accessible by way
of quantum dots. The biological tattoo/charagma will certify compliance and thus allow
them to enter any store, arena, school, public/government buildings and parks, airlines,
hospital, or place of employment. The governments will be quick to say that they will not
?mandate? compliance, however, through the strong ties of P3?s (Public Private Partnerships)
pressure will be placed on businesses, schools, hospitals, restaurants etc. to mandate that
one must show proof of vaccination to enter in order to maintain public safety and stop the
spread of those dreaded ?mutations? which you know will be carried around only by those
who didn?t take the vaccine? TAKE HEED.
A large percentage of the world?s population will take this vaccine. Those who don?t will be
targeted and made to separate from society (See our live stream about us coming out of
?Egypt? once again). Governments might not come right out and say that it is mandated at
first, but they will cause the private sector to do so through financial coercion.
Revelat ion 13:16-18 – King Jam es Version
16And he causet h all, both small and great, rich and poor, free and bond, to receive a mark in
their right hand, or in their foreheads:
17And that no man might buy or sell, save he that had the mark, or the name of the beast, or
the number of his name.
We?ve covered why we believe this is the mark spoken of in Revelation. We have provided you
with a great deal of medical, scientific, and technological data over many months of in-depth
live streams and insightful Entangled magazines to conclude that this DOES change the
Concerning the Lamb?s Book of Life, I believe scripture will relay it best. If you agree that this
new form of medical/technological treatment will change and defile God?s original human
design and method for fighting sickness and disease, please read below:
Revelat ion 13:8,KJV:
“And all that dwell upon the earth shall worship him, whose names are not written in the
book of life of the Lamb slain from the foundation of the world.”
Revelat ion 17:8, KJV:
?The beast that thou sawest was, and is not; and shall ascend out of the bottomless pit, and
go into perdition: and they that dwell on the earth shall wonder, whose names were not
written in the book of life from the foundation of the world, when they behold the beast that
was, and is not, and yet is.?
Revelat ion 20:12-15, KJV:
?And I saw the dead, small and great, stand before God; and the books were opened: and
another book was opened, which is the book of life: and the dead were judged out of those
things which were written in the books, according to their works. 13 And the sea gave up the
dead, which were in it; and death and hell delivered up the dead, which were in them: and
they were judged every man according to their works. 14 And death and hell were cast into
the lake of fire. This is the second death.15 And whosoever was not found written in the book
of life was cast into the lake of fire.?
Revelat ion 21:27, KJV: ?And there shall in no wise enter into it any thing that defileth, neither
whatsoever worketh abomination, or maketh a lie: but they which are written in the Lamb’s
book of life.?
The body will be ?defiled? and rendered ?desolate? once the permanent gene changes take
place. These modifications begin the moment the mRNA injection enters the body. There is
no turning back. mRNA immediately undertakes a replication process that alters our very
molecular/cellular structure. It is very different from the attenuated virus?used in
vaccinations of the past. This changes the way your body recognizes and fights infection and
disease. The body may very well turn and begin to attack itself.
Please pray in earnest about the decision you make. This is for eternity. The mainstream
media will never tell you this. God will! We are ?leaving Egypt? or the world?s current system.
We will work and live outside of the world?s system of commerce. The physical mark, will put in
place an identification and tracking system connected to commerce ? buying and selling. The
biological/genetic markers permanently alter God?s original human design. This He takes issue
We enjoy and appreciate your friendship. We will face the days ahead together. Utilizing our
God-given power through the Holy Spirit, we can and will upset the plans of the enemy in the
spiritual realm that has its outworking in our carnal world. We do not ever fight with physical
weapons of warfare, but with spiritual knowledge and power that can cripple demonic
strongholds!!! You know how to do this? now USE it wisely.
With much love,
Wit hin HIV-1, a Lent ivirus, a genus (above species and below fam ily) of
ret roviruses (a t ype of virus t hat insert s a copy of it s RNA genom e int o t he
DNA of a host cell) t here exist s a t hird st rand of DNA. This is referred t o in
t he lit erat ure as a cent ral DNA Flap [Mont agnier, et al. 2000]).
Im plicat ions of a Third St rand of DNA Wit hin SARS-CoV-2
and It s Vaccines
Discovered wit hin t he m RNA genom ic sequence of SARS-CoV-2 is t he
presence of 16 genom ic fragm ent s of HIV-1 (HIV Man-Manipulat ed
Coronavirus Genom e Evolut ion Trends [Mont agnier, et al. 2020]).
Video illust rat ing t he basic com ponent s of a
Lent ivirus em ploying HIV as an exam ple. Click
on arrow or t he above im age of a Lent ivirus.
French virologist Luc Ant oine Mont agnier, who was awarded a
Nobel prize in Physiology in 2008 along wit h Françoise
Barré-Sinoussi and Harald zur Hausen for discovering of t he HIV
virus, has now spoken out . Mont agnier was a researcher at t he
prest igious Past eur Inst it ut e in Paris causes m alaria, are found in
t he coronavirus’s genom e.
Addit ional references t o t he discovery wit hin t he m RNA genom ic
sequence of SARS-CoV-2 of 16 genom ic fragm ent s of HIV-1.
The research t hat Mont agnier refers t o was post ed on t he science
websit e Biorxiv January 31, 2020, and has since been wit hdrawn.
Mont agnier said: “We were not t he first since a group of Indian
researchers t ried t o publish a st udy which showed t hat t he
com plet e genom e of t his coronavirus [has] sequences of anot her
virus, which is HIV.”
The researchers wrot e: “We found 4 insert ions in t he spike
glycoprot ein (S) which are unique t o t he 2019-nCoV and are not
present in ot her coronaviruses.
Mont agnier said t he coronavirus had escaped in an “indust rial
accident ” while Chinese scient ist s at t he Wuhan cit y laborat ory
were t rying t o develop a vaccine against HIV.10 “In order t o
insert an HIV sequence int o t his genom e, m olecular t ools are
needed, and t hat can only be done in a laborat ory,” said
Im port ant ly, am ino acid residues in all t he 4 insert s have
ident it y or sim ilarit y t o t hose in t he HIV-1 gp120 or HIV-1
Gag … The finding of 4 unique insert s in t he 2019-nCoV, all
of which have ident it y /sim ilarit y t o am ino acid residues
in key st ruct ural prot eins of HIV-1 is unlikely t o be
fort uit ous in nat ure.” COVID-19 Derives From a Failed HIV
Vaccine, Says Mont agnier In a separat e appearance on t he
French podcast Pourquoi Doct eur, also April 17.
In a paper Mont agnier and Perez published on t he Cent er for
Open Science in April 2020, t hey writ e: “Using our propriet ary
bio-m at hem at ic approach we are able t o evaluat e t he level of
cohesion and organizat ion of a genom e; … we t hen searched in
t his genom e for possible t races of HIV or even SIV [relat ed
sim ian im m unodeficiency virus].
However, we dem onst rat e how and why a new region including
4 HIV1 HIV2 Exogenous Inform at ive Elem ent s radically
dist inguishes all COVID-19 st rains from all SARS and Bat st rains
… … a cont iguous region represent ing 2.49% of t he whole
COVID-19 genom e is 40.99% m ade up of 12 diverse EIE
originat ing from various st rains of HIV SIV ret roviruses … a
novel long region of around 225 nucleot ides, appears t o us t o
be t ot ally new: t his region is com plet ely absent in ALL SARS
genom es, whereas it is present and 100% hom ologous for all
COVID-19 genom es list ed in NCBI or GISAID COVID_19 genom ic
A first publicat ion report s t he discovery of 6 HIV SIV RNA pieces.”
The HIV and SIV elem ent s t hat Mont agnier and Perez det ect ,
called Exogenous Inform at ive Elem ent s, or EIEs, provide t he basis
of t heir t heory t hat COVID-19 is not a sim ple derivat ive of SARS
and bat -relat ed viruses. They writ e: “A m ajor part of t hese 16 EIE
already exist ed in t he first SARS genom es as early as 2003.
More About Mont agnier and Perez’s Theory. Aft er in-dept h
sequencing of relat ed genom es from m any different count ries,
regions of count ries and t im e periods using t heir propriet ary
biom at hem at ic approach, Mont agnier and Perez say t heir
research enabled t hem t o: “? dem onst rat e how and why a new
region including 4 HIV/SIV EIE radically dist inguishes all COVID-
19 st rains from all SARS and Bat st rains.”
Ot her Researchers Agree Wit h Mont agnier and Perez. Since
Mont agnier ‘s com m ent s t o French m edia, ot her researchers have
agreed t hat COVID-19 appears m anm ade, wit h insert ions t hat hint
at lab const ruct ion. In June 2020, research published in t he
Quart erly Review of Biophysics m akes sim ilar claim s.
“We show t he non-recept or dependent phagocyt ic general m et hod
of act ion t o be specifically relat ed t o cum ulat ive charge from
insert ed sect ions placed on t he SARS-CoV-2 Spike surface in
posit ions t o bind efficient ly by salt bridge form at ions; and from
blast ing t he Spike we display t he non hum an-like epit opes from
which Biovacc-19 has been down-select ed.”
Norwegian scient ist Birger Sørensen and Brit ish oncologist Angus
Dalgleish refer t o COVID-19 as a “chim eric virus” and writ e:
While conceding t he Quart erly Review of Biophysics assert ions
were cont roversial, t he scient ific websit e Minerva wrot e t hat t he
science should be pursued.
In an int erview wit h Minerva about his recent cont ent ious
research, he says:
?We have exam ined which com ponent s of t he virus are
especially well suit ed t o at t ach t hem selves t o cells in hum ans.
And we have done t his by com paring t he propert ies of t he virus
wit h hum an genet ics.
“Minerva has read a draft of t he art icle, and has aft er an
overall assessm ent decided t hat t he findings and
argum ent s do deserve public debat e, and t hat t his
discussion cannot depend ent irely on t he publicat ion
process of scient ific journals.”
Like Mont agnier, Sørensen’s background is HIV research
work and he launched a new im m unot herapy for HIV in
2008 t hat was acclaim ed.
End reference art icle
The significance of t he cent ral DNA flap is t o ensure t he ent ire genom e
com prising t he Lent ivirus HIV-1 is successfully im port ed int o t he nucleus
of t he t arget host cell. There exist s however, only 16 fragm ent s of t he
HIV-1 viral genom e wit hin t he single st rand m RNA of SARS-CoV-2. In t his
case, t he lent iviral t rait s of nuclear ent ry and int egrat ion wit h t he host
cell DNA rem ain int act as a chim eric genom e of SARS-CoV-2 and HIV-1.
By way of reverse t ranscript ion (RT), a m RNA based vaccine for SARS-CoV-2
t ranscribes t wo st rands of DNA, referred t o as com plem ent ary DNA (cDNA).
Then, in t ranslat ing a prot ein, t he m RNA m olecules leave t he cell nucleus
and ent er t he cyt oplasm t o synt hesize individual prot eins.
A vaccine consist ing of m RNA reverses t he norm al biological sequence of
event s known as t ranscript ion. Typically, double-st randed DNA t ranscribes
(copies) t o single st rand m olecules of RNA, which in t urn t ranslat es a
Sequence of event s
Click on arrow t o begin. Opens in a new browser, click t hrough slides
using arrows at t he bot t om of t he new page.
The presence of 16 genom ic fragm ent s of HIV-1 provides t he gain of
funct ion t o t he viral genom e of SARS-CoV-2 as illust rat ed wit hin t his
slideshow. The act ions of SARS-CoV-2 are now t he sam e as for HIV it self.
Replicat ion of HIV slideshow.
Due t o t he inclusion of 16 HIV-1 fragm ent s wit hin t his double st rand
cDNA, a t hird st rand m anifest s as a cent ral DNA flap. Addit ionallly,
codons of 3 DNA bases, represent t he genet ic code t hat t ransfers
inform at ion from genes t o m RNA wit hin t he nucleus, and t hen wit hin t he
cyt oplasm t RNA (t ransfer RNA) t ransfers t he genet ic code for t he
t ranslat ion of prot eins wit hin t he ribosom e.
Addit ionally, HIV envelope and Gag (Group-specific ant igen) genes in
SARS-CoV-2 have been codon opt im ized (opt im ize prot ein expression) t o
im prove t he expression of viral ant igens. Ant igens are a foreign
subst ance which induces an im m une response in t he body.
Last ly, published scient ific research st at es t he RNA of t he virus SARS-CoV-2
it self, reverse-t ranscribes and int egrat es int o t he hum an genom e.
Cent ral DNA flap
The enzym e ret roviral int egrase, produced by a Lent ivirus such as HIV-1,
plays an im port ant role int egrat ing t he viral DNA int o t he nucleus.
Covalent links (a chem ical bond t hat involves t he sharing of elect ron pairs
bet ween at om s) are form ed bet ween t he viral and host DNA, result ing in
a perm anent alt erat ion referred t o in t he lit erat ure as “a point of no
ret urn” for t he host cell. This form s a provirus, a perm anent carrier of
t he virus. Thus, t wo prim ary m echanism s are at work in t he changing of
t he host DNA. The cent ral DNA flap and t he enzym e ret roviral int egrase.
Two Int egrat ion Mechanism s
Lent iviruses possess a unique capacit y, am ong ret roviruses, t o replicat e
efficient ly in nondividing cells. They can of course, ent er cells undergoing
cell m it osis. Anot her m echanism at work in HIV-1 are pre-int egrat ion
com plexes (PIC), which are able t o cross t he double nuclear m em brane of
host cells. This is a pivot al event ensuring Lent iviruses are able t o
replicat e in nondividing cells.
A Third Int egrat ion Mechanism
Uncoat ing of t he pre-int egrat ion com plex at t he nuclear pore. Not e t he
presence of t he DNA flap m ediat ing t he folding of 2 com plem ent ary
st rands of DNA (cDNA). These reverse t ranscribed from t he Lent ivirus
SARS-CoV-2 cont aining t he 16 genom ic fragm ent s of HIV-1. The cDNA
ent ers t hrough t he nuclear pore com plex (NPC) and int o t he nucleus t o t he
right in t his im age.
The pre-int egrat ion com plex (PIC) is a nucleoprot ein com plex of viral
genet ic m at erial and associat ed viral and host prot eins which is capable
of insert ing a viral genom e int o a host genom e. The PIC form s aft er
uncoat ing of a viral part icle following ent ry t hrough t he out er plasm a
m em brane and int o t he host cell.
Pre-integration steps of HIV-1 replication. Events starting with HIV-1
binding to its main receptors on the target cell, CD4 and CCR5, and ending
with viral integration into the host cell’s genome are shown. Proteins
packaged into virions are shown; some of these proteins (MA, RT, IN, and
Vpr) find their way into the reverse transcription complex (RTC). RTC
becomes the pre-integration complex upon completion of reverse
The PIC form s aft er t he reverse t ranscript ion com plex (RTC) has reverse
t ranscribed (copying genet ic inform at ion) t he viral RNA (i.e. SARS-CoV-2
m RNA) int o DNA, referred t o as com plem ent ary DNA (cDNA). cDNA is
DNA synt hesized from a single-st randed RNA t em plat e, such as m RNA or
m icroRNA (m iRNA) in a react ion cat alyzed by t he enzym e reverse
t ranscript ase.
Com plem ent ary DNA (cDNA)
Com plem ent ary DNA (cDNA)
The PIC ent ers t he cellular nucleus t hrough t he nuclear pore com plex
(NPC). A NPC is a part of a large com plex of prot eins t hat spans t he
nuclear envelope, which is t he double m em brane surrounding t he nucleus.
The NPC ent ers t he nucleus wit hout disrupt ing t he nuclear envelope
(m em brane), t hus allowing t he lent ivirus HIV-1 t o replicat e in
non-dividing cells, as well as t hose undergoing cell m it osis.
Following nuclear ent ry, t he PIC’s DNA payload is int egrat ed int o t he
host cell’s DNA as a provirus.
Nuclear pore com plex (NPC)
A provirus is a virus genom e t hat is int egrat ed int o t he DNA of
anot her healt hy host cell. When a ret rovirus from out side t he body
(exogenous) invades a cell, such as t he RNA of t he Lent ivirus HIV-1, it
is reverse-t ranscribed (see lat er below) int o DNA by t he enzym e
reverse t ranscript ase.
It is t hen insert ed int o t he host genom e by t he enzym e int egrase. This is
t he process of t ransduct ion by which foreign DNA/RNA is int roduced int o a
cell by a virus or viral vect or (a vehicle t o art ificially carry foreign genet ic
m at erial int o anot her cell.
Reverse t ranscript ase is an enzym e used t o generat e com plem ent ary
DNA (cDNA) from an RNA t em plat e, a process t erm ed reverse
t ranscript ion. Reverse t ranscript ases are used by HIV-1 t o replicat e
t heir genom es, by ret rot ransponson m obile genet ic elem ent s t o
proliferat e wit hin t he host genom e. Ret rot ransponsons are a t ype of
genet ic com ponent t hat copy and past e t hem selves int o different
genom ic locat ions (t ransponson) by convert ing RNA back int o DNA
(cDNA) t hrough t he process of reverse t ranscript ion using RNA
t ransposit ion int erm ediat e.
Reverse t ranscript ase
Following ret rovirus infect ion, reverse t ranscript ase convert s viral
RNA int o proviral DNA, which is t hen incorporat ed int o t he DNA of
t he host cell in t he nucleus.
Encyclopædia Britannica, Inc.
The final product of HIV-1 reverse t ranscript ion is a linear DNA
m olecule bearing in it s cent er a st able 99 nucleot ide-long plus st rand
overlap, here referred t o as t he cent ral DNA flap. The dist inct ive
feat ures of Lent iviral reverse t ranscript ion account for t he unique
capacit y of Lent iviruses, am ong ret roviruses, t o replicat e in
The final product : Cent ral DNA flap
HIV-1 reverse t ranscript ion and int egrat ion of t he provirus.A
DNA flap is form ed during reverse t ranscript ion. There is
evidence t hat t he pre-int egrat ion com plex is t ransport ed t oward
t he nucleus via t he m icrot ubule net work.
Whereas t he proviruses of m ost ret roviruses are ent irely double
st rand DNA (dsDNA), t hose of HIV and ot her lent iviruses have a short
t riple-st randed sequence known as a cent ral DNA flap. This com es
about because t here are t wo init iat ion sit es for (+) DNA synt hesis; as
well as t he polypurine t ract (PPT) t oward t he 3?end of t he virus
genom e, t here is also a cent ral PPT wit hin t he pol region. Synt hesis of
t he (+) DNA init iat ed at t he 3?PPT st ops soon aft er reaching t he (+)
DNA init iat ed at t he cent ral PPT, result ing in a short overlapping DNA
sequence. This DNA flap plays a vit al role in t he early st ages of
Aft er reverse t ranscript ion has been com plet ed, t he pre-int egrat ion
com plex (PIC) which cont ains host prot eins as well as virus prot eins, is
t ransport ed int o t he nucleus. There is evidence t hat t ransport t oward
t he nucleus t akes place on t he m icrot ubule net work. Most
ret roviruses can product ively infect only if t here is breakdown of t he
nuclear m em branes. The pre-int egrat ion com plex of HIV, however, can
ent er an int act nucleus, such as t hat of a rest ing T cell or a
m acrophage, and is t ransport ed t hrough a nuclear pore com plex
The viral int egrase and cell enzym es are involved in t he int egrat ion of
t he provirus int o a cell chrom osom e; cell enzym es rem ove t he DNA flap
and repair t he gap. There is evidence t hat int egrat ion of t he provirus in
a rest ing m em ory CD4 T cell m ay result in a lat ent infect ion. Lat ent ly
infect ed cells can provide a reservoir of infect ion t hat is significant for
t he survival of t he virus in individuals receiving ant i-ret roviral drug
t herapy. In m any cells, t hough, provirus int egrat ion is t he prelude t o a
product ive infect ion in which t wo phases of gene expression can be
Laborat ory result s est ablish t hat t he cent ral init iat ion by t he cent ral
DNA flap of reverse t ranscript ion is necessary for HIV-1 replicat ion in
nondividing as well as proliferat ing cells. The cent ral DNA flap of HIV-1,
creat ed by cent ral init iat ion and t erm inat ion st eps during reverse
t ranscript ion, is necessary for HIV-1 pre-int egrat ion com plexes (PICs) t o
ent er t he host cell nucleus.
In t he absence of t his cent ral DNA flap, viral DNA nuclear im port is
severely im paired at a st age im m ediat ely preceding or during t he
t ranslocat ion of HIV-1 DNA t hrough t he nuclear pore. Thus, wit hout t he
t hird st rand DNA flap, all of t he HIV-1 DNA is unable t o ent er t he
nucleus. It is t he key det erm inant for nuclear im port of t he HIV-1
The original m echanism of HIV-1 nuclear im port is t he crucial role of t his
t hree-st randed DNA st ruct ure, t he cent ral DNA flap, in t his process.
HIV-1 possesses a com plex reverse t ranscript ion st rat egy, creat ing a
DNA flap at t he cent er of a single st rand of HIV-1 DNA m olecules. It is
t he det erm inant of t he nuclear im port of t he HIV-1 genom e, and it s
capacit y t o infect nondividing t arget cells. The lack of t he DNA flap
leads t o a virus t hat is alm ost noninfect ious in dividing and nondividing
The presence of a DNA flap at t he cent er of t he genom e is found in all
lent iviruses. The ent ire process of com plem ent ary DNA (cDNA)
synt hesis from m essenger RNA (m RNA) is com plet ed prior t o
t ranslocat ion of t he HIV pre-int egrat ion com plex (PIC) t hrough t he
nuclear pore com plex (NPC), and int o t he nucleus for int egrat ion
t hrough covalent linking wit h t he host DNA.
The single-st randed m RNA of SARS-CoV-2 cont ains 16 genom ic
fragm ent s of HIV-1. These code for specific gain of funct ion purposes.
In t his case, ensuring t he ent ry of t he SARS-CoV-2 virus int o t he host
DNA by ut ilizing t he inherent cent ral t hird-st randed DNA flap of HIV-1.
Alt hough t his appears count er-int uit ive, it m ust be kept in m ind wit h
respect t o SARS-CoV-2 and it s m RNA-based vaccines, t he nat ural process
has been reversed given t he product ion of DNA (cDNA) from m RNA. The
nat ural process involves DNA first t ranscribing t o RNA, wit h RNA
secondarily t ranslat ing prot eins.
Given t his flap is only 99 nucleot ides in lengt h, and not a com plet e
linear st rand, it is labeled as a flap, Hence, cDNA is st ill considered as
t wo com plet e linear st rands of t he original m RNA delivered by t he
vaccines, having t ranscribed t hem t hrough em ploym ent of t he enzym e
reverse t ranscript ase.
The m RNA based vacccines reverse t ranscribe t o cDNA in t he cyt osol
wit hin t he surrounding out er plasm a m em brane of t he cell.
Consequent ly, out side t he m em brane of t he nucleus. The cent ral DNA
flap (t hird st rand of DNA) is part of t his cDNA.
What is not appreciat ed is t he presence and funct ion of t his cent ral
DNA flap wit hin t he m RNA based vaccines. As st at ed before, what is
unique about lent iviruses, specifically HIV-1, is t his cent ral DNA flap.
It s norm al biological funct ion is t o m ediat e t he folding of t he t wo
linear st rands of cDNA, while incorporat ing t he enzym e int egrase.
In keeping wit h t he aforem ent ioned reversal of norm al biological
orders, is t he subject of vect ors. In t his inst ance, t he use of a vect or. A
t ool com m only used by m olecular biologist s t o deliver genet ic
m at erials int o cells. A t ransport vehicle.
The DNA based vaccines t ranscribe t o m RNA. Therefore, t he ent iret y
of t he processes out lined above apply t o t hem as well. The only
difference is t he order of occurance. In t his, t hese vaccines follow t he
nat ural biological sequence of DNA t ranscribing t o RNA.
This, for t he t ranslocat ion of t he SARS-CoV-2 viral genom es t hrough
t he nuclear pore com plex (NPC) t o covalent ly bond wit h t he host DNA.
The cent ral DNA flap ensures t he t wo st rands of cDNA are com pact
enough t o fit t hrough one of t he 1,000 pores of t he double-layered
nuclear m em brane.
SARS-CoV-2 t he virus, act ing as a vect or for 16 genom ic fragm ent s of
HIV-1 is necessit at ed by t he lack of a fully int act viral genom ic sequence
for HIV-1. The part ial genet ic inform at ion of HIV-1 is incorporat ed wit hin
t he overall genom ic sequence of SARS-CoV-2 it self. Thus, wherever t he
virus goes, so t oo t he 16 genom ic fragm ent s of HIV-1. Where t hese m ove,
t he virus SARS-CoV-2 m oves.
There are t wo orders t o consider here, incorporat ing m id-st ream , a
role reversal. First ly, SARS-CoV-2 t he virus, act ing as a vect or for 16
genom ic fragm ent s of HIV-1. Secondly, t he reversal, 16 HIV-1
fragm ent s act ing as a vect or for t he SARS-CoV-2 virus it self.
The copies, known as com plem ent ary, are of t he ent ire m RNA genom ic
sequence of SARS-CoV-2. Again, t his sequence cont ains each of t he 16
genom ic fragm ent s of HIV-1. Their presence is for gain of funct ion
purposes. Specifically, t o ensure int egrat ion wit h t he host DNA of t he
viral genet ic m at erial of SARS-CoV-2. It accom plishes t his fucnt ion as a
nat ural lent iviral act ion of HIV-1.
Because t his is an int act sequence of m RNA, bot h in t he form of t he virus
it self, and as a vaccine (bot h m RNA and DNA-based), it m oves as a unit .
Whet her ent ering t hrough t he out er plasm a cell m em brane, or t hrough
t he cyt osol wit hin, and t hrough t he double m em brane of t he nucleus,
t he genet ic m at erials rem ain t oget her. In fact , t hey replicat e t oget her,
em ploying t he enzym e reverse t ranscript ase, t o express cDNA.
The sequences responsible for form at ion of t he DNA flap are found at t he
cent er of all lent iviral genom es. This cent ral posit ion has developed due
t o t he form at ion of t he pre-int egrat ion com plexes (PICs). The left and
right arm s of t he linear cDNA (reverse t ranscribed from t he m RNA of
SARS-CoV-2) m olecule fold around t his cent ral flap. This is necessary for
efficient t ranslocat ion of t his cDNA t hrough t he nuclear pore com plexes
Edit or ‘s Not e: It should be em phasized, t he
cont ract ing of SARS-CoV-2 does not indicat e a
concurrent cont ract ing of HIV-1. The m RNA
sequence of SARS-CoV-2 cont ains only port ions of
t he ent ire HIV-1 virus it self.
The individual genom ic fragm ent s of HIV-1 were select ively chosen for
t heir specific funct ion of enabling t he t ranslocat ion t hrough t he nuclear
pore com plexes (NPCs) of t he rem aining genet ic m at erials com prising
SARS-CoV-2. The so-called “gain of funct ion” for t he virus.
The presence of t his cent ral DNA flap wit hin all lent iviruses, explains t he
purpose for t he inclusion of 16 genom ic fragm ent s of HIV-1 wit hin t he
overall genom ic m RNA sequence of SARS-CoV-2. The int ent is for t he
perm anent alt erat ion of t he host DNA t he virus t hus infect s. The sam e
holds t rue for any and all vaccines for SARS-CoV-2 and it s m ut at ions. This
is t he funct ion of m olecular biology.
Over t he last five years, t here has been an enorm ous increase in t he
am ount of research int o RNA m odificat ions, a field called
epit ranscript om ics.
Epit ranscript om ics includes all t he biochem ical m odificat ions of RNA
(t he t ranscript om e) wit hin a cell. This involves all funct ionally relevant
changes t o t he t ranscript om e t hat do not involve a change in t he
ribonucleot ide sequence. Thus, t he epit ranscript om e can be defined as
t he ensem ble of such funct ionally relevant changes. The t ranscript om e
is t he set of all RNA t ranscript s, including coding and non-coding, in an
individual or a populat ion of cells.
In t he case of SARS-CoV-2, t he 16 genom ic fragm ent s of HIV-1 found
wit hin it s m RNA genom ic sequence, are represent at ive as an ensem ble
of funct ionally relevant changes t o t he virus. These, again, are referred
t o in t he lit erat ure as “gain of funct ion” changes.
SARS-CoV-2 RNA reverse-t ranscribed and int egrat ed int o t he
hum an genom e
Addit ional specific research on t he int egrat ion of t he SARS-CoV-2 RNA int o
t he hum an genom e can be found here:
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