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J Investig Med High Impact Case Rep ; 9: 23247096211040626, 2021.
Article in English | MEDLINE | ID: covidwho-1371944


Epstein-Barr virus (EBV), a member of the herpes virus family, is a causative agent for infectious mononucleosis in young adults. It has an asymptomatic and subclinical distribution in about 90% to 95% of the world population based on seropositivity. EBV is associated with various lymphomas, nasopharyngeal carcinoma, and in immunocompromised states can give rise to aggressive lymphoproliferative disorders. Symptomatic patients mostly present with mild hepatitis, rash, oral symptoms, lymphadenopathy, and generalized malaise. Recently with the COVID-19 (coronavirus disease-2019) pandemic, hepatitis has been found to be related to acute EBV and cytomegalovirus reactivation versus acute infection in the absence of other major causes. We describe a case of EBV coinfection in a patient with resolving mild COVID-19 infection.

COVID-19/complications , Coinfection , Epstein-Barr Virus Infections/complications , Herpesvirus 4, Human , SARS-CoV-2 , Herpesvirus 4, Human/pathogenicity , Humans , Male , Middle Aged
PLoS Pathog ; 17(4): e1009041, 2021 04.
Article in English | MEDLINE | ID: covidwho-1231262


Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus with latent and lytic cycles. EBV replicates in the stratified epithelium but the nasopharynx is also composed of pseudostratified epithelium with distinct cell types. Latent infection is associated with nasopharyngeal carcinoma (NPC). Here, we show with nasopharyngeal conditionally reprogrammed cells cultured at the air-liquid interface that pseudostratified epithelial cells are susceptible to EBV infection. Donors varied in susceptibility to de novo EBV infection, but susceptible cultures also displayed differences with respect to pathogenesis. The cultures from one donor yielded lytic infection but cells from two other donors were positive for EBV-encoded EBERs and negative for other lytic infection markers. All cultures stained positive for the pseudostratified markers CK7, MUC5AC, α-tubulin in cilia, and the EBV epithelial cell receptor Ephrin receptor A2. To define EBV transcriptional programs by cell type and to elucidate latent/lytic infection-differential changes, we performed single cell RNA-sequencing on one EBV-infected culture that resulted in alignment with many EBV transcripts. EBV transcripts represented a small portion of the total transcriptome (~0.17%). All cell types in the pseudostratified epithelium had detectable EBV transcripts with suprabasal cells showing the highest number of reads aligning to many EBV genes. Several restriction factors (IRF1, MX1, STAT1, C18orf25) known to limit lytic infection were expressed at lower levels in the lytic subcluster. A third of the differentially-expressed genes in NPC tumors compared to an uninfected pseudostratified ALI culture overlapped with the differentially-expressed genes in the latent subcluster. A third of these commonly perturbed genes were specific to EBV infection and changed in the same direction. Collectively, these findings suggest that the pseudostratified epithelium could harbor EBV infection and that the pseudostratified infection model mirrors many of the transcriptional changes imposed by EBV infection in NPC.

Epithelial Cells/virology , Epstein-Barr Virus Infections/virology , Host-Pathogen Interactions/immunology , Nasopharyngeal Neoplasms/virology , Carcinoma/metabolism , Carcinoma/virology , Epithelial Cells/metabolism , Epithelium/metabolism , Epithelium/virology , Epstein-Barr Virus Infections/metabolism , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/pathogenicity , Humans , Nasopharyngeal Carcinoma/virology , RNA, Viral/genetics
Rev Med Virol ; 31(6): e2228, 2021 11.
Article in English | MEDLINE | ID: covidwho-1126517


Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used as antiviral agents for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. We performed a systematic review to examine whether prior clinical studies that compared the effects of CQ and HCQ to a control for the treatment of non-SARS-CoV2 infection supported the use of these agents in the present SARS-CoV2 outbreak. PubMed, EMBASE, Scopus and Web of Science (PROSPERO CRD42020183429) were searched from inception through 2 April 2020 without language restrictions. Of 1766 retrieved reports, 18 studies met our inclusion criteria, including 17 prospective controlled studies and one retrospective study. CQ or HCQ were compared to control for the treatment of infectious mononucleosis (EBV, n = 4), warts (human papillomavirus, n = 2), chronic HIV infection (n = 6), acute chikungunya infection (n = 1), acute dengue virus infection (n = 2), chronic HCV (n = 2), and as preventive measures for influenza infection (n = 1). Survival was not evaluated in any study. For HIV, the virus that was most investigated, while two early studies suggested HCQ reduced viral levels, four subsequent ones did not, and in two of these CQ or HCQ increased viral levels and reduced CD4 counts. Overall, three studies concluded CQ or HCQ were effective; four concluded further research was needed to assess the treatments' effectiveness; and 11 concluded that treatment was ineffective or potentially harmful. Prior controlled clinical trials with CQ and HCQ for non-SARS-CoV2 viral infections do not support these agents' use for the SARS-CoV2 outbreak.

Chikungunya Fever/drug therapy , Chloroquine/therapeutic use , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Hydroxychloroquine/therapeutic use , Infectious Mononucleosis/drug therapy , Severe Dengue/drug therapy , Warts/drug therapy , Alphapapillomavirus/drug effects , Alphapapillomavirus/immunology , Alphapapillomavirus/pathogenicity , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Chikungunya Fever/immunology , Chikungunya Fever/pathology , Chikungunya Fever/virology , Chikungunya virus/drug effects , Chikungunya virus/immunology , Chikungunya virus/pathogenicity , Dengue Virus/drug effects , Dengue Virus/immunology , Dengue Virus/pathogenicity , HIV/drug effects , HIV/immunology , HIV/pathogenicity , HIV Infections/immunology , HIV Infections/pathology , HIV Infections/virology , Hepacivirus/drug effects , Hepacivirus/immunology , Hepacivirus/pathogenicity , Hepatitis C, Chronic/immunology , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Herpesvirus 4, Human/drug effects , Herpesvirus 4, Human/immunology , Herpesvirus 4, Human/pathogenicity , Humans , Infectious Mononucleosis/immunology , Infectious Mononucleosis/pathology , Infectious Mononucleosis/virology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severe Dengue/immunology , Severe Dengue/pathology , Severe Dengue/virology , Treatment Outcome , Warts/immunology , Warts/pathology , Warts/virology
Nature ; 590(7844): 29-31, 2021 02.
Article in English | MEDLINE | ID: covidwho-1038200