SARS-CoV-2 proteins and anti-COVID-19 drugs induce lytic reactivation of an oncogenic virus

  1. Jungang Chen
  2. Lu Dai
  3. Lindsey Barrett
  4. Jennifer James
  5. Karlie Plaisance-Bonstaff
  6. Steven R. Post
  7. Zhiqiang Qin

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Abstract

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of Coronavirus Disease-2019 (COVID-19), a respiratory disease, has infected almost one hundred million people since the end of 2019, killed over two million, and caused worldwide social and economic disruption. Because the mechanisms of SARS-CoV-2 infection of host cells and its pathogenesis remain largely unclear, there are currently no antiviral drugs with proven efficacy. Besides severe respiratory and systematic symptoms, several comorbidities increase risk of fatal disease outcome. Therefore, it is required to investigate the impacts of COVID-19 on pre-existing diseases of patients, such as cancer and other infectious diseases. In the current study, we report that SARS-CoV-2 encoded proteins and some currently used anti-COVID-19 drugs are able to induce lytic reactivation of Kaposi’s sarcoma-associated herpesvirus (KSHV), one of major human oncogenic viruses, through manipulation of intracellular signaling pathways. Our data indicate that those KSHV + patients especially in endemic areas exposure to COVID-19 or undergoing the treatment may have increased risks to develop virus-associated cancers, even after they have fully recovered from COVID-19.

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  3. Version published to 10.1038/s42003-021-02220-z
  4. ScreenIT

    SciScore for 10.1101/2020.10.02.324228: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Western blot: Total cell lysates (20 μg) were resolved by 10% SDS–PAGE, transferred to nitrocellulose membranes, and immunoblotted with antibodies to SARS-CoV-2 S or N (Abcam), phosphor (p)-p65/total (t)-p65, p-ERK/t-ERK, p-JNK/t-JNK, p-p38/t-p38 and GAPDH as a loading control (Cell Signaling).
    p)-p65/total (t)-p65, p-ERK/t-ERK,
    suggested: None
    p-JNK/t-JNK
    suggested: None
    p-p38/t-p38
    suggested: None
    GAPDH
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    HEK293T (Human embryonic kidney 293T) cells and KSHV+ PEL cell line, BCP-1, were purchased from American Type Culture Collection (ATCC) and cultured as recommended by the manufacturer.
    HEK293T
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    There are a few limitations and unanswered questions in our study. Firstly, we did investigate using the live virus of SARS-CoV-2 because we do not have access. However, since the S and N proteins represent major and abundant structural proteins of SARS-CoV-2, it will not be surprising to see the live virus display similar effects on this induction. Secondly, we do not have clinical data to support our findings yet. However, this is difficult because the KSHV test is not a routine examination in COVID-19 patients. Further, the seroprevalence of KSHV infection in the general population of the United States is less than 10%, but in most of sub-Saharan Africa, the overall seroprevalence is more than 50% (Mesri et al., 2010). Since mother-to-child transmission of KSHV through saliva is the most common route of transmission, there is a high prevalence of early childhood KSHV infection in some areas (Cao et al., 2014; El-Mallawany et al., 2019; Newton et al., 2018). Moreover, KS has now become one of the most common overall childhood cancers throughout the central, eastern, and southern regions of Africa (El-Mallawany et al., 2018). As we know, children are also susceptible to SARS-CoV-2 infection, although with milder symptoms and lower mortality rates (Bogiatzopoulou et al., 2020). In addition, the seroprevalence of KSHV infection is greatly increased in other sub-populations such as HIV-infected individuals, homosexual men and organ transplant recipients (Mesri et al., 2010). In...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  5. Version published to 10.1101/2020.10.02.324228v1 on bioRxiv