SARS-CoV-2 spike protein and mRNA can get inside the human nucleus

A study showed that the SARS-CoV-2 spike protein and its messenger RNA could get inside the nucleus of human cells.

The study, Nuclear translocation of spike mRNA and protein is a novel feature of SARS-CoV-2, was peer-reviewed and published in Frontiers in Microbiology in January 2023.

Nuclear translocation is unique to SARS-CoV-2 and not seen on other human coronaviruses, including Severe Acute Respiratory Syndrome virus (SARS-CoV) and the Middle East Respiratory Syndrome coronavirus (MERS).

The research also found an intriguing way the spike protein and its mRNA could enter the nucleus.

How the spike protein and mRNA enter the nucleus

What is inside the SARS-CoV-2 not found in other coronaviruses that give its spike protein and mRNA the unique capability to enter the nucleus?

The study showed that the translocation of the SARS-CoV-2 S mRNA and the spike protein is due to the nuclear localization signals (NLS) motif called “PRRARSV,” not found in other human coronaviruses.

Nuclear localization signals (NLS) are short peptides (short amino acid chains) that mediate the transport of proteins from the cytoplasm into the nucleus.

They found that Sequence Insertion 4 (IS4) “NSPR” created the “PRRARSV” in the Spike protein, which was unique to SARS-CoV-2.

We found that the IS4 “NSPR” created a pat7 NLS “PRRARSV” in the S protein, which was unique to SARS-CoV-2.

NSPR and PRRARSV represent amino acid sequences. Each letter represents an amino acid. A chain of amino acids represents a peptide that can have a biological function.

The study demonstrated that PRRARSV made the spike protein and mRNA get inside the nucleus of human cells.

NSPR is intriguing because it is connected to the “RRAR.” “RRAR” in the spike protein of the SARS-CoV-2 is the hinge or the furin cleavage site (FCS) that makes the SARS-CoV-2 more infectious and more pathogenic by attaching to the ACES2 receptors in the body’s different cells.

The image below shows that NSPR and PRRARSV are combined into NSPRRARSV inside the red rectangle. The sequence of the furin cleavage site (PRRA) can be seen inside the combination.

Source: Nuclear translocation of spike mRNA and protein is a novel feature of SARS-CoV-2. Front. Microbiol., 26 January 2023.

A paper by Harrison and Sachs has proposed that the furin cleavage site (PRRA) is evidence that the SARS-CoV-2 may be laboratory made and needs further investigation.

The image below compares the sequences of several animal and human coronaviruses. Only the Wuhan-Hu-1, the ancestral SARS-CoV-2, is the only one with the furin cleavage site (FCS) on the list.[2]

Source: A call for an independent inquiry into the origin of the SARS-CoV-2 virus. Proc Natl Acad Sci U S A. 2022 May 24

Back to the study, airway epithelial cells which mimic in vivo human airway epithelium were infected with SARS-CoV-2.[1]

Under an RNAscope and using immunofluorescence analysis, they found Spike mRNA and S protein were present in the nucleus of the SARS-CoV-2-infected cells.

The image below shows the Spike messenger RNA in red. The Spike protein is in cyan, and the nucleus is in blue. Note: Multiplicity of Infection (MOI) is the ratio of SARS-CoV-2 to infection targets (cells).

Even with only a tiny amount (1%) of the spike mRNA inside the nucleus, this is still highly unusual.

The nuclear translocation of S mRNA is highly unusual because there have been few previous reports of S mRNA nuclear translocation and no information on the mechanism of nuclear translocation.

A higher percentage of Spike protein translocated into the nucleus than S mRNA. This means the Spike protein more likely mediates Spike mRNA nuclear translocation because S mRNA nuclear translocation was always associated with the S protein.

In their discussion, the authors said their results support a previous machine learning-based study showing that the SARS-CoV-2 RNA genome and sub-genomic RNAs can be translocated in the host cells’ mitochondria and nucleus (Wu et al., 2020).

What is the significance of the spike protein and mRNA inside the nucleus?

The findings do not necessarily mean that the mRNA in the COVID-19 shots can integrate with the human DNA.

Thus, our results lack sufficient detail to contribute to the discussion of the controversial scientific topic of whether there is any possibility of SARS-CoV-2 genome integration into the host DNA.

If you want proof that the mRNA can be integrated into the human genome, read SARS-CoV-2 RNA Reverse Transcribed to Human DNA.

In it, I discussed the study by Zhang et al. Reverse-transcribed SARS-CoV-2 RNA could integrate into the genome of cultured human cells and be expressed in patient-derived tissues.

One possible consequence of the spike protein and its mRNA inside the nucleus may lead to the evasion of the host’s immune response.

I found a study from Japan by Tomita et al. (not related to SARS-CoV-2) that showed that extrinsic mRNA could exert some functions like upregulating antiapoptotic gene expression, migration activity, and interferon-γ production without getting translated into DNA.

Take Away Message

The ability of the spike protein and its messenger RNA to get into the nucleus is a unique feature of SARS-CoV-2 not found in other human coronaviruses.

Just like the furin cleavage site, it may be responsible for the increased pathogenicity of SARS-CoV-2.

Is it laboratory made? Does it contribute to the complications of the COVID injections? Future studies that will use this study’s results will confirm that.

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References:

Sattar et al. Nuclear translocation of spike mRNA and protein is a novel feature of SARS-CoV-2. Front. Microbiol., 26 January 2023. Volume 14 – 2023 | https://doi.org/10.3389/fmicb.2023.1073789
Harrison NL, Sachs JD. A call for an independent inquiry into the origin of the SARS-CoV-2 virus. Proc Natl Acad Sci U S A. 2022 May 24;119(21):e2202769119. doi: 10.1073/pnas.2202769119. Epub 2022 May 19. PMID: 35588448; PMCID: PMC9173817.

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