Alterations in Cellular Gene Expression Due to Co-Infection With Kaposi's Sarcoma-Associated Herpesvirus and SARS-CoV-2: Implications for Disease Severity

Jungang Chen; Jiaojiao Fan; Priyangi A Malaviarachchi; Steven R Post; Zhen Lin; Xuming Zhang; Zhiqiang Qin

doi:10.1002/jmv.70149

Alterations in Cellular Gene Expression Due to Co-Infection With Kaposi's Sarcoma-Associated Herpesvirus and SARS-CoV-2: Implications for Disease Severity

J Med Virol. 2025 Jan;97(1):e70149. doi: 10.1002/jmv.70149.

Authors

Jungang Chen¹, Jiaojiao Fan¹, Priyangi A Malaviarachchi², Steven R Post¹, Zhen Lin³, Xuming Zhang², Zhiqiang Qin¹

Affiliations

¹ Department of Pathology, Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
² Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
³ Department of Pathology, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, Louisiana, USA.

PMID: 39740042
DOI: 10.1002/jmv.70149

Abstract

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 pandemic, has resulted in over 7 million confirmed deaths. In addition to severe respiratory and systematic symptoms, several comorbidities increase the risk of fatal outcomes. Therefore, it is essential to investigate the impact of COVID-19 on pre-existing conditions in patients, such as cancer and other infectious diseases. Recent clinical studies have reported the reactivation of human herpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), in severe COVID-19 patients or vaccinated individuals. To support these clinical observations, we established a KSHV/SARS-CoV-2 co-infection system in A549-hACE2 cells. Our findings indicate that co-infection with live SARS-CoV-2 sharply induces KSHV lytic reactivation. Transcriptomic analysis revealed significant changes in global cellular gene expression in KSHV-infected A549-hACE2 cells, both with and without SARS-CoV-2 co-infection. These data provide a molecular basis for understanding whether patients with pre-existing oncogenic herpesvirus infections are at increased risk for more severe COVID-19 or for developing virus-associated cancers even after full recovery from COVID-19.

Keywords: COVID; KSHV; SARS‐CoV‐2; co‐infection.

MeSH terms

A549 Cells
COVID-19* / complications
COVID-19* / virology
Coinfection* / virology
Gene Expression
Gene Expression Profiling
Herpesviridae Infections / complications
Herpesviridae Infections / virology
Herpesvirus 8, Human* / genetics
Herpesvirus 8, Human* / physiology
Humans
SARS-CoV-2* / genetics
SARS-CoV-2* / pathogenicity
Sarcoma, Kaposi / virology
Severity of Illness Index
Virus Activation

Grants and funding

This work was supported by the Arkansas Bioscience Institute, the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000. S.R.P. was supported by a National Cancer Institute grant R01CA261258. Z.L. was supported by a National Cancer Institute grant R01CA261258, a National Institute of General Medical Sciences COBRE grant P20GM121288, a U.S.-Japan Cooperative Medical Sciences Program Collaborative Award from the National Institute of Allergy and Infectious Diseases and CRDF Global (grant number DAA3-19-65602-1), a Ladies Leukemia League research grant, a Tulane school of medicine faculty research pilot grant, and a Carol Lavin Bernick faculty grant.