38 Vaccines
38.1 Origin of diseases
Pendergrass & Vettese Abstract
Edward Jenner took the long view. His 1798 treatise on vaccination, which reported a revolutionary new method of preventing smallpox, opened with a medical philosophy of history rather than a description of symptoms or a review of existing treatments. “The deviation of Man from the state in which he was originally placed by Nature seems to have proved to him a prolific source of Diseases,” he explained. By this he meant that infectious disease ultimately resulted from human and animal intermingling since the agricultural revolution, an insight anthropologists and epidemiologists have since confirmed. The majority of human pathogens are ultimately zoonoses, originating not at the dawn of the human species but in the relatively recent past. Measles likely evolved from the bovine disease rinderpest seven thousand years ago. Influenza may have started about forty-five hundred years ago with the domestication of waterfowl. Jenner’s own specialty, smallpox, probably originated four thousand years ago in eastern Africa when a gerbil virus jumped to the newly domesticated camel and then to humans. The New World’s Indigenous nations cultivated countless crops but practiced little animal husbandry, allowing them to live relatively free of disease before 1492. European conquest succeeded in a large part thanks to the invaders’ pathogenic armory of measles, typhus, tuberculosis, and smallpox, which decimated Indigenous populations by 90 percent over the succeeding centuries.
38.2 mRNA
DW
Claim: mRNA vaccines manipulate human DNA
DW: False
It is easy to get DNA and RNA confused, two similar abbreviations that relate to genetic material. But they’re very different.
DNA contains the genetic blueprint that determines our bodies’ various traits. Viruses such as SARS-CoV-2 have RNA that stores their genetic material.
But RNA is also found in the human body, and plays a role in protein synthesis.
Viruses tap into this mechanism to reproduce in human cells. The human body, however, recognizes these intruders by their protein spike, producing antibodies and t-cells to fight off the virus.
RNA vaccinations inject only one element of the SARS-CoV-2 virus into the human body, namely mRNA, containing the blueprint to produce its spike protein. The human immune system then kicks into action, forming antibodies against the pathogen.
No human or virus RNA, however, ever enters the cell nucleus. This means it does not get in contact with our genetic material. After serving its purpose, human cells then break down the RNA.
A scientific study published in December 2020 claims the genetic material from the SARS-CoV-2 virus could manipulate human DNA through the reverse transcriptase, an enzyme that transcribes RNA into DNA, which can enter the cell nucleus. The study in question has not yet been peer-reviewed and is hotly debated.
Virologist David Baltimore from the California Institute of Technology won the Nobel Prize for his role in discovering reverse transcriptase.
Science magazine quoted him describing the new work and findings as “impressive” and “unexpected.” However, he noted that the work showed only that fragments of the COVID-19 virus genome integrate that couldn’t produce infectious particles and represented a biological “dead end.”
“It is also not clear if, in people, the cells that harbor the reverse transcripts stay around for a long time or they die,” Baltimore said. The work raises a lot of interesting questions.”
Waldemar Kolanus, who headsLife & Medical Sciences Institute (LIMES) at Bonn University, doubts the findings are relevant for the actual vaccine. Speaking to DW, he said the structure of mRNA has been deliberately altered for vaccines so as to prevent cells instantly breaking them down.”Most likely, it cannot be reverse transcribed.” As such, mRNA vaccines are much safer with regard to such processes than actual virus genomes, he says.
Zhang
Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests have been widely reported in patients after recovery, yet these patients most commonly are non-infectious. Here we investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome and that transcription of the integrated sequences might account for PCR-positive tests. In support of this hypothesis, we found chimeric transcripts consisting of viral fused to cellular sequences in published data sets of SARS-CoV-2 infected cultured cells and primary cells of patients, consistent with the transcription of viral sequences integrated into the genome. To experimentally corroborate the possibility of viral retro-integration, we describe evidence that SARS-CoV-2 RNAs can be reverse transcribed in human cells by reverse transcriptase (RT) from LINE-1 elements or by HIV-1 RT, and that these DNA sequences can be integrated into the cell genome and subsequently be transcribed. Human endogenous LINE-1 expression was induced upon SARS-CoV-2 infection or by cytokine exposure in cultured cells, suggesting a molecular mechanism for SARS-CoV-2 retro-integration in patients. This novel feature of SARS-CoV-2 infection may explain why patients can continue to produce viral RNA after recovery and suggests a new aspect of RNA virus replication.
From Comment Section
Mellissa Booth Chimeric sequence reads that the researchers found in the sequence databases are likely artifacts from the preparation of the RNA libraries. These chimera artifacts are a common phenomenon in total RNA sequence library construction from complex samples whether the source material is from humans, soil, sewage, ocean water, etc., and these artifacts end up in sequence databases. The other lab bench experiments DO NOT show that SARS-CoV-2 RNA is reverse transcribed to DNA, transported into the nucleus and then integrated into the host genome under NORMAL conditions. However, there are assays that could answer the question about viral integration. The authors could collect samples from infected patients that are still shedding virus but are non-infectious (as they mention in their summary) and perform Southern Blot analysis to determine if viral sequences have indeed been integrated into the host genome. And ultimately, IF the researchers find integration under normal conditions, the next questions follow: Are infected cells persistent? Do these integrated elements propagate in host cells? These are the questions that get to their hypothesis about purported viral integration elements being responsible for persistent detection of virus in non-infectious, post-COVID patients.
Mar Your argument only addresses their initial screening of public datasets. They do show integration in vitro when they extract cell genomic DNA and do PCR. Southern blot is not necessary.
Zhang (2020) SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome (Preprint Not Peered) (pdf)
Viral Shedding
When an individual gets infected by a respiratory virus like SARS-CoV-2, the virus particles will bind to the various types of viral receptors, particularly the angiotensin-converting enzyme 2 (ACE2) receptors in the case of SARS-CoV-2, that line the respiratory tract.
Throughout this ongoing process, infected individuals, who may not yet be experiencing any of the viral symptoms, are shedding viral particles while they talk, exhale, eat, and perform other normal daily activities.
Under normal circumstances, viral shedding will not persist for more than a few weeks; however, as researchers gain a more in-depth understanding of the viral clearance of SARS-CoV-2, they have found that certain populations will shed this virus for much longer durations.
In fact, a growing amount of evidence indicates that the viral shedding of SARS-CoV-2 begins before a patient is symptomatic, peaks at the point of or shortly after symptom onset and can continue to be released even after the individual’s symptoms have been resolved.
The duration of viral shedding can be used to categorize the infectivity of a person; therefore, this information is crucial in implementing effective infection prevention strategies, such as appropriate quarantine durations and mask requirements.
Currently, SARS-CoV-2 infection is confirmed with a positive polymerase chain reaction (PCR) test that can be conducted regardless of whether an individual is experiencing symptoms. Through such PCR tests, viral shedding of SARS-CoV-2 has been found to have a median duration of 12 to 20 days, with a persistence that can reach up to 63 days after initial symptom onset.
The viral shedding of SARS-CoV-2 from the gastrointestinal (GI) tract does not appear to have any correlation with disease severity.
There remains uncertain information on the proportion of SARS-CoV-2 cases that are asymptomatic. It is unclear as to whether these “asymptomatic” cases are truly asymptomatic in the sense that these infected individuals will never experience any of the viral symptoms, or are rather presymptomatic, meaning that these individuals had no symptoms at the time of their positive PCR test but eventually developed symptoms later.
During both the SARS outbreak of 2002 and 2003, as well as during the current pandemic, researchers hypothesized that live viral particles present within fecal matter moving through sewage pipes could infect individuals through aerosols or droplets.
SARS-CoV-2 RNA has been detected commonly in patient feces. However, as of yet more evidence is needed to assess the quantities of virus in fecal matter and its replication abilities in order to determine whether fecal-oral viral transmission is possible.
Cuffari. What is Viral Shedding
Viral Integration and consequences on Host Gene Expression
Upon cell infection, some viruses integrate their genome into the host chromosome, either as part of their life cycle (such as retroviruses), or incidentally. While possibly promoting long-term persistence of the virus into the cell, viral genome integration may also lead to drastic consequences for the host cell, including gene disruption, insertional mutagenesis and cell death, as well as contributing to species evolution. This review summarizes the current knowledge on viruses integrating their genome into the host genome and the consequences for the host cell.
Viral genome integration into the host genome is a hallmark of retroviruses, as it is a mandatory step in the retroviral life cycle and a prerequisite for productive infection. Upon integration, the retrovirus will persist in the infected cell for its entire lifespan, and will affect host gene expression depending on the integration site. Furthermore, if retroviral infection and integration occurs in the germline, the provirus will be transmitted to the progeny, and will thus contribute shaping the genome of future generations. This is the case of the so called “endogenized” retroviruses or endogenous retroviruses (ERV).
The site of the viral integration event can have multiple consequences for the host, as well as for the virus itself. Indeed, viral integration can lead to cell death or proliferation as a result of insertional mutagenesis. However, integration can also lead to consequences for the virus, i.e. active production or transcriptional silencing, a process also called latency that is key to establish viral persistence. Finally, integration in the germline can contribute shaping the host genome and participate in species evolution.
Retrovirus
Retroviruses have undergone quite an explosion in our knowledge in about the last 40 years. The term “retrovirus” means it behaves backwards from the original way that we all think about genetics, which is that DNA makes RNA, and RNA makes protein. So retroviruses have an RNA genome, and when they get into cells that RNA is reverse-transcribed into DNA, so it goes backwards. The DNA is then inserted into the genome of the cell, so when the cell divides, it copies this, and it begins to express RNA. Some of that RNA is translated into proteins, which are needed to package the retrovirus. And another of those RNAs is the RNA genome that goes into those packaging materials and is excreted from the cell and goes on to infect other cells. So there are many different kinds of retroviruses. Now, the most famous one right at the moment is the human immunodeficiency virus which causes acquired immunodeficiency syndrome, or AIDS. But there are many different kinds of retroviruses that are associated with diseases, including cancer, leukemia, and AIDS, obviously. Finally, retroviruses have been tamed for use in gene therapy, so it is possible to take out all of the genes that allow the retrovirus to replicate itself and replace that with a gene that the particular cell that you’re interested in is missing. And so using the integrating ability of a retrovirus, you can actually take something that could ordinarily harm people and turn it into something that can be used as a therapeutic vehicle to make them better.