Cytomegalovirus, Epstein-Barr virus and human herpesvirus 8 salivary shedding in HIV positive men who have sex with men with controlled and uncontrolled plasma HIV viremia: a 24-month longitudinal study.

BACKGROUND: This longitudinal study described Cytomegalovirus (CMV) DNA, Epstein-Barr (EBV) DNA and human herpesvirus 8 (HHV-8) DNA asymptomatic salivary shedding in HIV-positive men who have sex with men (MSM). We aimed to 1-analyze frequency and persistence of herpesvirus shedding, 2-correlate herpesvirus positivity and HIV viroimmunological parameters and 3-assess the association between HIV-RNA suppression and herpesvirus replication. METHODS: Herpesvirus DNA was tested with an in-house real-time PCR in 2 salivary samples obtained at T0 and T1 (24 months after T0). HIV-RNA was evaluated in the 24 months prior to T0 and in the 24 months prior to T1; MSM were classified as successfully suppressed patients (SSPs), viremic patients (VPs) and partially suppressed patients (PSPs). EBV DNA load was classified as low viral load (EBV-LVL, value ≤10,000 copies/ml) and as high viral load (EBV-HVL,> 10,000 copies/ml). Mann-Whitney U test tested the difference of the median between groups of patients. Chi-squared test and Fisher's exact test compared categorical variables according to the frequencies. Kruskal-Wallis test compared continuous data distributions between levels of categorical variables. RESULTS: Ninety-two patients (median CD4+ count 575 cells/mm3, median nadir 330 CD4+ cells/mm3) were included: 40 SSPs,33 VPs and 19 PSPs. The more frequently single virus detected was EBV, both at T0 and at T1 (in 67.5 and 70% of SSPs, in 84.8 and 81.8% of VPs and in 68.4 and 73.7% of SPSs) and the most frequently multiple positivity detected was EBV + HHV-8. At T1, the percentage of CMV positivity was higher in VPs than in SSPs (36.4% vs 5%, p < 0.001), the combined shedding of HHV-8, CMV and EBV was present only in VPs (15.1%, p = 0.01 respect to SSPs) and no VPs confirmed the absence of shedding found at T0 (vs 17.5% of SSPs, p = 0.01). EBV-HVL was more frequent in VPs than in SSPs: 78.6% at T0 (p = 0.03) and 88.9% at T1 (p = 0.01). CONCLUSIONS: The relationship between uncontrolled plasma HIV viremia and CMV, EBV, and HHV-8 shedding is multifaceted, as demonstrated by the focused association with EBV DNA load and not with its frequency and by the persistent combined detection of two oncogenic viruses as EBV and HHV-8 regardless of HIV virological control.

Oropharyngeal group A streptococcal colonization disrupts latent Epstein-Barr virus infection.

Epstein-Barr virus (EBV) infects >90% of the human population within the first 2 decades of life and establishes reversible latent infection in B cells. The stimuli that lead to switching from latent to lytic EBV infection in vivo are still elusive. Group A streptococci (GAS) are a common cause of bacterial pharyngotonsillitis in children and adolescents and colonize the tonsils and pharynx of up to 20% of healthy children. Thus, concomitant presence of EBV and GAS in the same individual is frequent. Here, we show that EBV carriers who are colonized with GAS shed EBV particles in higher numbers in their saliva, compared with EBV carriers not colonized with GAS. Messenger RNA levels of the master lytic regulatory EBV gene BZLF1 were more frequently detected in tonsils from EBV carriers colonized with GAS than from EBV carriers not colonized. Heat-killed GAS, potentially mimicking GAS colonization, elicited lytic EBV in latently infected lymphoblastoid cell lines (LCLs) partially via Toll-like receptor 2 triggering, as did purified GAS peptidoglycan. Thus, colonization by GAS might benefit EBV by increasing the EBV load in saliva and thereby enhancing the likelihood of EBV spread to other hosts.

Diagnostic performance of saliva RT-PCR test as a diagnostic tool and its utility in the detection of SARS-CoV-2 shedding with different patient characteristics: Prospective observational study.

BACKGROUND: Salivary shedding of SARS-CoV-2 is a known entity and its role has been established in transmission of the disease. The present study was performed to evaluate the duration of viral shedding in saliva in COVID-19 patients and its variation among symptomatic and asymptomatic patients with or without co-morbidities. METHODS: The present prospective observational study was conducted at the COVID-19 care hospital associated with primary to tertiary care in New Delhi, India. A total of 124 COVID-19 confirmed cases enrolled in two phases (January-March 2021; April-June 2021) who consented for 48hrly saliva and nasopharyngeal swab (NPS) specimens till discharge from the hospital for SARS-CoV-2 detection were included. The specimens obtained were tested for SARS-CoV-2 by Real-Time PCR. RESULTS: The sensitivity and the specificity of RT-PCR on saliva were 81.7 â€‹% and 85.0 â€‹%, respectively. The sensitivity of saliva-based PCR was comparable in symptomatic and asymptomatic patients (81.6 â€‹% vs 82.1 â€‹%). The sensitivity of saliva-based PCR markedly increased in the second phase of enrollment as compared to the first phase (92.6 â€‹% vs 78.5 â€‹%) indicating higher level of salivary shedding by the delta variant of SARS-CoV-2. The sensitivity of PCR on saliva was the highest up to day seven of illness. The median duration of RNA shedding in saliva was comparable among the symptomatic and asymptomatic patients. The severity of the disease was not associated with the duration of SARS-CoV-2 shedding in saliva. CONCLUSIONS: SARS-CoV-2 shedding in saliva continued till seven days in large number of patients including asymptomatic patients. Saliva is non-inferior to NPS specimen in the diagnosis of SARS-CoV-2. Saliva specimen is recommended as a good alternate to NPS for SARS-CoV-2 testing.

Epstein - Barr Virus Salivary Shedding in Patients with Acute Infectious Diseases: A Pilot Study.

Background: Epstein-Barr virus (EBV) is a widely disseminated herpesvirus for which antibodies have been demonstrated in over 90% of adults worldwide. After subclinical primary EBV infections, as well as after infectious mononucleosis, the virus can be shed in saliva for a prolonged period of time. Aim: Diseases and disorders that can induce EBV salivary shedding include mental disorders and sex, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, malaria and HIV infection. Since the occurrence of EBV in saliva during acute infectious diseases has not yet been systematically researched, we aimed to investigate the possible relationship between acute infectious diseases and salivary shedding of EBV. Material and methods: This pilot cross-sectional study included consenting adults hospitalized for acute infectious conditions and their peers free of acute infectious diseases. A total of 40 patients with acute infectious diseases were enrolled, along with 41 adults free of acute infections. Peripheral venous blood samples for serodiagnosis and saliva samples for EBV PCR testing were collected from both groups. We fitted logit and general linear models to proportions and to ln (viral copy counts) to generate adjusted proportions and geometric mean values in the two groups of subjects. We used SAS for Windows 9.4. Results: The most common acute infectious disease was COVID-19 pneumonia, followed by hemorrhagic fever with renal syndrome. Crude proportions of people with positive serological test results and those with saliva viral shedding were similar in the two groups. Conclusions: The presented preliminary data do not indicate acute infectious conditions as a marked "contributor" in increasing salivary EBV shedding.

Salivary shedding of herpesviruses in renal transplant recipients.

AIM: The aim of the present study was to describe the salivary shedding of human herpesviruses (HHV) in renal transplant recipients and to observe the oral manifestations in this group. METHODS: A prospective case-control study was conducted with a study group of 20 renal transplant recipients and a control group of 20 non-transplanted, immunocompetent individuals. Clinical examination evaluated the presence of drug-induced gingival overgrowth (DIGO), salivary flow, and caries. Stimulated saliva was collected from both groups, with HHV being detected by using real-time polymerase chain reaction. RESULTS: The mean age of the study group was 45.90 ± 9.89 years, with 55% (11/20) being female, 60% (12/20) being Caucasian, 65% (13/20) having a deceased donor, and 70% (14/20) having used tacrolimus as the main immunosuppressive drug. Renal transplant recipients had shedding of more herpesviruses compared to the control group, with the exception of HHV-7. Statistical significance was found for herpes simplex virus-1 (HSV-1) (P = 0.017) and cytomegalovirus (P = 0.035). DIGO was observed in seven patients (35%), with 35% (7/20) presenting with decreased salivary flow and four (20%) reporting xerostomia. CONCLUSION: Renal transplant recipients excreted herpesviruses more often than control individuals, especially HSV-1. Decreased salivary flow and xerostomia were more frequent in patients who used tacrolimus, whereas those who used cyclosporine had more cases of DIGO.