Thread by @vipintukur

Can a respiratory #virus infection confer #immunity against the other #respiratory virus? A much-debated issue in the virus immunology for many decades. What is the probable immune mechanism & does it indeed exist? What is the evidence for & against this hypothesis? 1/

It is hypothesized that a respiratory virus infection confers immunity against the same and other respiratory viruses for a short time, perhaps a few weeks. This immunologic mechanism, known as #heterosubtypic ‘temporary non-specific immunity’ 2/

This immune protection is associated with activation of the innate immune response to viral infection mediated by the release of Type I #interferons (IFN) & other cytokines that have broad protective effects against a range of viruses 3/

Besides, viruses are known to interfere with the circulation of other viruses. For example, there is evidence that the circulation of #Rhinovirus in the community interferes & decreases the spread of seasonal & pandemic #influenza viruses 4/

pubmed.ncbi.nlm.nih.gov/19822124/

Last year, me & @dr_puneet wrote a piece for @EditorIndPed on the similar theme 5/

pubmed.ncbi.nlm.nih.gov/32525495/

Now, a recent study by the @YaleMed have reignited this debate. The researchers find that exposure to the #rhinovirus, the most frequent cause of the common cold, can protect against infection by the #SARSCoV2 virus @Yale @VirusesImmunity 6/

rupress.org/jem/article/21…

The study demonstrates that prior infection with a #rhinovirus protects against the replication of SARSCoV2 as a result of the intact antiviral response that was already present at the time of the infection by SARS-CoV-2 7/
pubmed.ncbi.nlm.nih.gov/34128960/

#SARSCoV2 #RNA increases exponentially, with a doubling time of ∼6 h, and infection induces a robust ISG response in organoids by day 4 after infection 8/

the researchers infected airway epithelial organoid cultures with human rhinovirus and evaluated the effect that this virus had on the expression of #ACE2. Following the rhinovirus infection, the truncated form of ACE2 known as dACE2 was found to increase significantly 9/

In a 2nd study, they infected the same type of organoid cultures with #SARSCoV2, w/ or w/out a prior infection by the #rhinovirus. Three days after the initial infection, rhinovirus-infected cells were found to induce the expression of #ISGs 10/

Comparatively, SARS-CoV-2 infected organoids that were not previously exposed to rhinovirus experienced a dramatic increase in their viral load 11/

Furthermore, SARS-CoV-2 infected organoid cultures that were previously infected with rhinovirus exhibited a significant increase in IFN1 levels as compared to organoid cultures that were not previously infected with the rhinovirus 12/

At early parts in the infection, pre infected cultures were found to exhibit a greater expression of ISGs as compared to organoids that were not previously infected with the rhinovirus 13/

They found that at the start of infection with #SARSCoV2, the viral #RNA replicates at an exponential rate that induces #ISG expression levels....... 14/

......When previously infected by the #rhinovirus, the induction of #ISG expression is much more rapid, thereby allowing the innate immune system to inhibit SARSCoV2 replication more quickly 15/

Overall, the studies performed by them demonstrate that prior infection with a #rhinovirus protects against the replication of #SARSCoV2 as a result of the intact antiviral response that was already present at the time of the infection by SARS-CoV-2 16/

This graphic summarizes the key messages. Heterologous innate immunity creates a subset of individuals refractory to infection during periods of high respiratory virus circulation....... 17/

A. Virus 1 induces mucosal #IFN, which creates a refractory period following infection during which ISGs are elevated & the host is protected from a 2nd viral infection (red shading). After ISGs return to baseline, the host is again susceptible & can be infected with virus 2
18/

(B) During periods of high resp virus circulation, a fraction of the population is refractory to infection at any given time due to ISG activation from a recent infection (red shaded figures) 19/

Thus, heterologous innate immune protection could mitigate against viral transmission at times of high respiratory virus circulation 20/

There are hidden interactions between viruses that we don’t quite understand, and the above findings are a piece of the puzzle we are just now looking at! @Yale @YaleMed @florian_krammer @trvrb @profvrr 21/end

news.yale.edu/2021/06/15/com…