Human Herpesvirus Research Articles

HHV-8-associated diseases in transplantation: A case report and narrative review focused on diagnosis and prevention.

Human herpes virus 8 (HHV-8) or Kaposi sarcoma herpesvirus (KSHV) is an opportunistic oncovirus that causes multiple pathologic entities. We present a case of fatal HHV-8-associated multisystem illness with disseminated Kaposi sarcoma and HHV8-associated lymphoproliferative disorder with systemic inflammation. We conducted a narrative review of the literature on HHV-8 in transplantation with a goal of illuminating the spectrum of HHV-8-associated diseases in this vulnerable population, modes of disease transmission, and the potential role for donor and recipient screening. HHV-8-associated KS, primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and KSHV inflammatory cytokine disorder (KICS) may affect transplant recipients; with the exception of KS, these conditions are rare but carry high morbidity and mortality. HHV-8-associated diseases have diverse and protean manifestations in transplant recipients, with potentially fatal outcomes. HHV-8 seroprevalence among organ donors and the magnitude of risk for donor-derived HHV-8 infection or clinically significant disease remain unknown and require further study.

Immunophenotyping and viral studies in pityriasis lichenoides et varioliformis acuta lesions.

The underlying pathogenesis of pityriasis lichenoides et varioliformis acuta (PLEVA) remains unclear, although immunologic injury and viral etiology have been suggested. To evaluate and expand the immunophenotype of PLEVA and to search for possible viral pathogens. Formalin-fixed, paraffin-embedded specimens of 20 patients with PLEVA and 9 patients with common inflammatory dermatoses (ID) were studied for immunophenotyping and for human herpesvirus (HHV) 1 and 2, cytomegalovirus (CMV), HHV-8, parvovirus B19, and Epstein-Barr virus (EBV) immunohistochemistry. The presence of HHV-6, HHV-7, and enteroviruses was assayed molecularly. The numbers of CD8+ T cells and T-cell intracellular antigen-1 (TIA-1)+ cells were statistically significantly higher in PLEVA compared to the ID group. Immunohistochemistry for human HHV-1 and HHV-2, CMV and HHV-8, parvovirus B19, and in situ hybridization for EBV were all negative. There was molecular evidence for HHV-7 in only one PLEVA case (5%). Molecular studies for HHV-6 and enterovirus involvement were negative in all the PLEVA specimens. The predominant T-cell infiltrate in PLEVA is dominated by CD8+ cells, and by increased numbers of TIA1+ cells, which may indicate a cytotoxic T-cell damage to the epidermis. Viral presence was not detected.

Molecular detection and genotyping of human herpes virus 8 in blood donors in Congo.

Human herpesvirus 8 (HHV8) is rarely studied in Congo, despite its prevalence in Africa. Among healthy individuals, HHV-8 does not always lead to a life-threatening infection; however, in immunocompromised individuals, it could lead to more severe disease. The distribution of HHV-8 genotypes varies depending on ethnicity and geographic region. A prospective cross-sectional study included 265 samples from healthy blood donors from the National Blood Transfusion Center in Brazzaville, with an average age of 35 years, with extremes ranging from 18 to 60 years. After DNA extraction, a nested PCR was carried out for molecular detection, followed by genotyping by amplification of specific primers. In this study, 4.9% were positive for molecular detection of HHV-8 DNA. All HHV-8 positive DNA samples that were subjected to genotyping by amplification with specific primers allowing discrimination of two major genotypes (A and B). Genotype A was identified in 5 (1.9%) samples and genotype B in 2 (0.7%) samples, indicating that both genotypes were predominant. The remaining viral DNA samples not identified as the major genotypes were classified as «indeterminate» and consisted of 6 (2.3%) samples. The results of the study suggest that Congo is an area where HHV-8 infection is endemic.

Evaluation of the AltoStar AM16 system for the quantitation of AdV, CMV and HHV-6 DNA from clinical specimens

The vulnerability of immunocompromised patients to common or opportunistic viral infections is particularly high. The quantitation of viral load in clinical specimens is important for the diagnosis and management of the infection and reactivation in this patient population, particularly transplant recipients. As the new regulation “IVDR” regarding in vitro diagnosis methods is about to come into effect in France, diagnostic laboratories have to implement methods and systems compatible with this new regulation. Technical performance of the AltoStar® Adenovirus (AdV), Cytomegalovirus (CMV) and human Herpesvirus-6 (HHV-6) DNA PCR Kits 1.5 was assessed on the AltoStar Automation system AM16 using reference kits in 146 clinical samples. Overall agreement in clinical specimens was 87.5 % (28/32), 96.8 % (62/64), 100 % (22/22), 100 % (28/28) and 92.8 % (26/28) for AdV, CMV (WB samples and other matrices), HHV-6 A&B respectively. Quantitative results were highly correlated and estimated to be equivalent within a 0.057–0.648 log-amount difference.We found that altona kits on The AltoStar AM16 system are suitable for clinical monitoring of AdV, CMV and HHV-6 in immunocompromised hosts.

Association between adeno-associated virus 2 and severe acute hepatitis of unknown etiology in Japanese children

IntroductionOutbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in Western countries in 2022. Previous studies found that adeno-associated virus 2 (AAV2) and its helper viruses, such as human adenovirus (HAdV) and human herpesvirus-6 (HHV-6), are frequently detected in patients with AHUE. However, the existence of hepatitis associated with AAV2 prior to AHUE outbreaks in 2022 had not yet been investigated. We aimed to investigate the association between AAV2 and pediatric acute hepatitis in Japanese children, as well as the incidence of AAV2-related hepatitis prior to 2022. MethodsPreserved blood samples obtained from 49 pediatric patients with acute hepatitis between 2017 and 2023 were retrospectively analyzed. Blood samples from 50 children with acute illnesses and 50 children with chronic conditions were used as controls. Viral DNA loads were quantitated using real-time PCR. ResultsAAV2 DNA was detected in 12% (6/49) of acute hepatitis cases but in only one acute illness and none of the chronic-condition control cases. The concentration of AAV2 DNA in the six acute hepatitis cases was higher than that in the acute-illness control case. Co-infection with one or more helper viruses, including HAdV, HHV-6, cytomegalovirus, and Epstein-Barr virus, was observed in five AAV2-positive cases. ConclusionsOur results indicated the sporadic occurrence of pediatric severe hepatitis associated with AAV2 infection in Japan prior to the AHUE outbreaks in 2022. Our findings suggest that co-infection with AAV2 and helper viruses plays a role in developing severe hepatitis.

Clinical Characteristics and Prognosis of Patients With Severe Pneumonia With Pneumocystis jirovecii Colonization: A Multicenter, Retrospective Study

BackgroundFor decades, the incidence and clinical characteristics of Pneumocystis jirovecii (P. jirovecii) colonization in patients with severe pneumonia was remained unclear. Research questionWhat are the clinical features and outcomes associated with P. jirovecii colonization in individuals diagnosed with severe pneumonia? Study design and methodsIn this multicenter, retrospective, matched study, severe pneumonia patients who underwent bronchoalveolar lavage clinical metagenomics from 2019 to 2023 in the ICUs of 17 medical centers were enrolled. Patients were diagnosed based on clinical metagenomics, pulmonary CT scans, and clinical presentations. Clinical data were collected retrospectively, and according to propensity score matching and Cox multivariate regression analysis, the prognosis of patients with P. jirovecii colonization was compared to that of P. jirovecii-negative patients. Results40% of P. jirovecii positive patients are considered to have P. jirovecii colonization. P. jirovecii colonization group had a higher proportion of patients with immunosuppression and a lower lymphocyte count compared to P. jirovecii-negative group. More frequent detection of cytomegalovirus, Epstein–Barr virus, human herpesvirus-6B, human herpesvirus-7, and torque teno virus in the lungs was associated with P. jirovecii colonization than with P. jirovecii negativity. By constructing two cohorts through propensity score matching, we incorporated codetected microorganisms and clinical features into a Cox proportional hazards model and revealed that P. jirovecii colonization was an independent risk factor for mortality in severe pneumonia patients. According to sensitivity analyses, which included or excluded codetected microorganisms, as well as patients not receiving TMP-SMX treatment, similar conclusions were reached. InterpretationImmunosuppression and a reduced lymphocyte count were identified as risk factors for P. jirovecii colonization in non-PCP patients. More frequent detection of various viruses was observed in P. jirovecii colonization patients, and P. jirovecii colonization was associated with an increased 28-day mortality in patients with severe pneumonia.

Clinical, Laboratory, and Imaging Characteristics of Tropheryma Whipplei Detection in Bronchoalveolar Lavage Fluid Using Next-Generation Sequencing: A Case-Control Study.

The aim of this study was to assess the prevalence of Tropheryma whipplei (TW) infection in the population and to investigate the clinical symptoms, as well as the laboratory and imaging characteristics of patients testing positive for TW using next-generation sequencing (NGS). A retrospective review was conducted on 1346 bronchoalveolar lavage fluid (BALF) samples collected between January 2021 and September 2023. The case group comprised patients with TW detected using NGS while the control group included 65 randomly chosen Gram-positive bacterial infection patients without TW. Comparative analyses were carried out on the basic demographics, laboratory parameters, and imaging findings between the two groups. Additionally, the case group underwent an in-depth examination of underlying diseases, pathogens, final diagnoses, treatment strategies. The case group comprised of 51 patients with TW, constituting 3.8% of the total. There was no significant difference in gender and age between the case and control groups (P = 0.84, P = 0.07). Symptoms such as coughing, expectoration, wheezing, fever, and hemoptysis are less commonly detected in the case group with a higher incidence of chest pain when compared to the control group (P >0.05). The case group exhibited decreased albumin levels and increased C-reactive protein and D-dimer levels compared to normal levels. Imaging findings in the case group commonly included nodules, patchy images, and interstitial changes, the most common underlying disease is cardiovascular disease, and the most frequently co-occurring pathogen is the human herpesvirus. Among the case group, 27 patients received a final diagnosis of pneumonia, and 3 patients clinically diagnosed with Whipple's disease demonstrated improvement in both symptoms and imaging after treatment. NGS revealed a relatively low overall detection rate of TW-positive patients using BALF. TW was more prevalent in middle-aged and elderly male patients characterized by symptoms such as cough, expectoration, shortness of breath, and fever. Chest imaging in these cases typically showed nodules and interstitial changes.

Combined Effect of Basic Antiherpetic Drugs with a New Inhibitor of the Terminase Complex of Herpes Simplex Virus Type 1 in Vero Cell Cultures.

Carriers of herpes simplex virus type 1 (HSV-1) account for more than 90% of the global population. Infection manifests itself in the formation of blisters and ulcers on the face or genitals and can cause blindness, encephalitis, and generalized infection. All first- and second-line modern antiherpetic drugs selectively inhibit viral DNA polymerase. The purine-benzoxazine conjugate LAS-131 ((S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine), which we have described earlier, uses the large subunit of the HSV-1 terminase complex as a biotarget and selectively inhibits HSV-1 reproduction in vitro. Basically new results were for the first time obtained to characterize the combined effect on human herpesvirus infection for LAS-131 used in combination with practically significant antiviral compounds, including the nucleoside analogs acyclovir (ACV), penciclovir (PCV), ganciclovir (GCV), brivudine (BVdU), iododeoxyuridine (IdU), and adenine arabinoside (Ara-A); the nucleoside phosphonate analog cidofovir (CDV); and the pyrophosphate analog foscarnet (FOS). A cytopathic effect (CPE) inhibition assay showed that the drug concentration that inhibited the virus-induced CPE by 50% decreased by a factor of 2 (an additive effect, FOS) or more (a synergistic effect; ACV, PCV, GCV, IdU, BVdU, Ara-A, and CDV) when the drugs were used in combination with LAS-131. Nonpermissive conditions for HSV-1 reproduction were thus created at lower drug concentrations, opening up new real possibilities to control human herpesvirus infection.

Seroprevalence of human herpes viruses in France, 2018–2022: a multilevel regression and poststratification approach

Background Information related to herpes simplex virus 1 and 2 (HSV-1 and 2), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) seroprevalence in France is either lacking, incomplete, or outdated, despite their public health burden. Method We used routinely collected serological data between 2018 and 2022 to estimate HSV-1, HSV-2, VZV, EBV, and CMV seroprevalence in France. To account for demographic differences between our analytic samples and the French population and get estimates for sparsely sampled districts and age classes, we used a multilevel regression and poststratification approach combined with Bayesian model averaging via stacking weights. Results The observed seroprevalence (number of positive tests/number of tests) were 64.6% (93,294/144,424), 16.9% (24,316/144,159), 93.0% (141,419/152,084), 83.4% (63,199/75, 781), and 49.0% (23,276/47,525), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV. Between 2018 and 2022, France had a model-based average (equal-tailed interval at 95%) expected seroprevalence equal to 61.1% (60.7,61.5), 14.5% (14.2,14.81), 89.5% (89.3,89.8), 85.6% (85.2,86.0), and 50.5% (49.3,51.7), respectively, for HSV-1, HSV-2, VZV, EBV, and CMV infections. We found an almost certain lower expected seroprevalence in Metropolitan France than in overseas territories for all viruses but VZV, for which it was almost certainly greater. The expected seroprevalences were likely greater among females for all viruses. Limitations Our results relied on the assumption that individuals were sampled at random conditionally to variables used to build the poststratification table. Implications The analysis highlights spatial and demographic patterns in seroprevalence that should be considered for designing tailored public health policies.

Postpartum Bilateral Nerve Palsy: A Harbinger for Preeclampsia?

Objective: To report a case of postpartum bilateral facial weakness that preceded the diagnosis of preeclampsia. Introduction: Bell’s palsy is a neuromuscular disorder that can cause paralysis or weakness of the face. It is the most common cause of unilateral facial weakness; however, bilateral weakness is rare. Bell’s palsy is one of the most common neuromuscular disorders observed in pregnancy, though the link between the two is not entirely clear. Proposed etiologies include reactivation of human herpes viruses, immune mediated inflammatory demyelination of the facial nerve, and microangiopathy as a result of systemic hypertension. There have been several case reports and studies suggesting a correlation between preeclampsia and Bell’s palsy. We present a rare case of postpartum bilateral Bell’s palsy in the setting of preeclampsia. Design: Case report. Results: Our patient is a 24 year-old G6P4116 Caucasian woman with no significant past medical history who presented with bilateral facial weakness and headache. She was postpartum day four from a spontaneous vaginal delivery of dichorionic diamniotic twins at 35 weeks at an outside hospital. She denied any elevated blood pressures during her pregnancy. Initially, on postpartum day two she had reported a severe headache that initially affected her occipital region bilaterally before migrating to her ears and forehead. At this time the patient was normotensive and was discharged home on analgesics. On postpartum day three, she returned to another emergency department with a worsening, severe headache. She was sent home with a diagnosis of anxiety. On postpartum day four, her symptoms persisted and she came to the emergency department at our facility. During our initial evaluation, her blood pressure was 170/98. She was admitted for severe preeclampsia and given IV magnesium and nifedipine. However, her headache persisted and she developed bilateral facial weakness, neck pain, and swelling. She reported that she was unable to move her face and had difficulty smiling. Her face was expressionless. She denied nausea, vomiting, dysphagia, double vision, gait disturbances, hearing loss, fever, shortness of breath, numbness, or tingling. She denied recent travel, sick contacts, or animal or tick bites. She was evaluated by neurology and her initial physical exam revealed intact cranial nerves, though the patient appeared to have difficulty squeezing her eyes shut and smiling. Periorbital edema was noted. Facial symmetry and sensation were intact bilaterally. She had difficulty saying the letter “P.” Her MRIs of both brain and cervical spine, chest x-ray, and lumbar puncture were all normal. Our working diagnoses included bilateral Bell’s palsy, Guillain-Barré and Miller-Fischer syndromes. The antibody panel drawn for Miller-Fischer syndrome subsequently resulted as negative. Our patient received three days of IVIG and was discharged on a week supply of prednisone 60mg with a taper thereafter. At discharge, she had severe bilateral facial droop. She was unable to puff out her cheeks or raise her eyebrows. Neurology recommended outpatient follow up. One month after discharge she had residual right sided facial droop, but the deficits of the left side of her face had mostly resolved. Discussion: Current literature suggests a correlation between preeclampsia and Bell’s palsy. There is some thought that elevated blood pressure leads to facial nerve compression secondary to edema or microemboli. One report suggested that the onset of Bell’s palsy antepartum or postpartum may be a predictor of preeclampsia. An English language PUBMED search revealed six case reports on bilateral Bell’s palsy in either the pregnant or postpartum state. Cases reported occurred in either the third trimester or within the first week postpartum. This was consistent with the onset of our patient’s symptoms during her first week postpartum. In one case, neurological symptoms preceded preeclampsia. Our patient complained of headaches and neck pain prior to having elevated blood pressures. Three of these cases included twin gestations, as did our case. Outcomes varied, with some patients seeing complete resolution of symptoms within weeks to others having recurring symptoms over a year. Providers should consider the relationship between preeclampsia and Bell’s palsy when treating pregnant or postpartum patients with new onset neurological symptoms. Pregnant and postpartum patients are at greater than three times increased risk for Bell’s palsy and have more severe symptoms and longer recovery times compared to the average population. It is important that obstetricians and gynecologists assess for signs of preeclampsia in pregnant or postpartum patients with concerns for Bell’s palsy, as well as refer patients for a complete neurological workup. Ultimately, more research is needed to further understand the relationship between preeclampsia and Bell’s palsy.

Postpartum Bilateral Nerve Palsy: A Harbinger for Preeclampsia?

Objective: To report a case of postpartum bilateral facial weakness that preceded the diagnosis of preeclampsia. Introduction: Bell’s palsy is a neuromuscular disorder that can cause paralysis or weakness of the face. It is the most common cause of unilateral facial weakness; however, bilateral weakness is rare. Bell’s palsy is one of the most common neuromuscular disorders observed in pregnancy, though the link between the two is not entirely clear. Proposed etiologies include reactivation of human herpes viruses, immune mediated inflammatory demyelination of the facial nerve, and microangiopathy as a result of systemic hypertension. There have been several case reports and studies suggesting a correlation between preeclampsia and Bell’s palsy. We present a rare case of postpartum bilateral Bell’s palsy in the setting of preeclampsia. Design: Case report. Results: Our patient is a 24 year-old G6P4116 Caucasian woman with no significant past medical history who presented with bilateral facial weakness and headache. She was postpartum day four from a spontaneous vaginal delivery of dichorionic diamniotic twins at 35 weeks at an outside hospital. She denied any elevated blood pressures during her pregnancy. Initially, on postpartum day two she had reported a severe headache that initially affected her occipital region bilaterally before migrating to her ears and forehead. At this time the patient was normotensive and was discharged home on analgesics. On postpartum day three, she returned to another emergency department with a worsening, severe headache. She was sent home with a diagnosis of anxiety. On postpartum day four, her symptoms persisted and she came to the emergency department at our facility. During our initial evaluation, her blood pressure was 170/98. She was admitted for severe preeclampsia and given IV magnesium and nifedipine. However, her headache persisted and she developed bilateral facial weakness, neck pain, and swelling. She reported that she was unable to move her face and had difficulty smiling. Her face was expressionless. She denied nausea, vomiting, dysphagia, double vision, gait disturbances, hearing loss, fever, shortness of breath, numbness, or tingling. She denied recent travel, sick contacts, or animal or tick bites. She was evaluated by neurology and her initial physical exam revealed intact cranial nerves, though the patient appeared to have difficulty squeezing her eyes shut and smiling. Periorbital edema was noted. Facial symmetry and sensation were intact bilaterally. She had difficulty saying the letter “P.” Her MRIs of both brain and cervical spine, chest x-ray, and lumbar puncture were all normal. Our working diagnoses included bilateral Bell’s palsy, Guillain-Barré and Miller-Fischer syndromes. The antibody panel drawn for Miller-Fischer syndrome subsequently resulted as negative. Our patient received three days of IVIG and was discharged on a week supply of prednisone 60mg with a taper thereafter. At discharge, she had severe bilateral facial droop. She was unable to puff out her cheeks or raise her eyebrows. Neurology recommended outpatient follow up. One month after discharge she had residual right sided facial droop, but the deficits of the left side of her face had mostly resolved. Discussion: Current literature suggests a correlation between preeclampsia and Bell’s palsy. There is some thought that elevated blood pressure leads to facial nerve compression secondary to edema or microemboli. One report suggested that the onset of Bell’s palsy antepartum or postpartum may be a predictor of preeclampsia. An English language PUBMED search revealed six case reports on bilateral Bell’s palsy in either the pregnant or postpartum state. Cases reported occurred in either the third trimester or within the first week postpartum. This was consistent with the onset of our patient’s symptoms during her first week postpartum. In one case, neurological symptoms preceded preeclampsia. Our patient complained of headaches and neck pain prior to having elevated blood pressures. Three of these cases included twin gestations, as did our case. Outcomes varied, with some patients seeing complete resolution of symptoms within weeks to others having recurring symptoms over a year. Providers should consider the relationship between preeclampsia and Bell’s palsy when treating pregnant or postpartum patients with new onset neurological symptoms. Pregnant and postpartum patients are at greater than three times increased risk for Bell’s palsy and have more severe symptoms and longer recovery times compared to the average population. It is important that obstetricians and gynecologists assess for signs of preeclampsia in pregnant or postpartum patients with concerns for Bell’s palsy, as well as refer patients for a complete neurological workup. Ultimately, more research is needed to further understand the relationship between preeclampsia and Bell’s palsy.

Frequency and clinical impact of viraemia in paediatric patients undergoing therapy for cancer

In contrast to transplant recipients, there is a paucity of data regarding frequency and clinical significance of viraemia in children receiving conventional chemotherapy. In a prospective observational study, we assessed the frequency of and clinical impact of viraemia with cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, human herpesvirus-6 (HHV6) and herpes-simplex virus 1/2 (HSV1/2) in paediatric cancer patients at diagnosis, at a routine examination during intensive chemotherapy, and during febrile neutropenia (FN). Seventy-nine patients (median age 6 years; 66 children with haematological malignancies) were included in the study. Overall, 362 blood samples were analysed, 72 from the time at diagnosis (11.1% with positive PCR result), 118 during a regular control after chemotherapy (11.0% positive), and 159 during FN (8.8% positive). The overall positivity rate was 9.6% (CMV 3.3%, HHV6 2.7%, HSV 2.2%, EBV 0.8% and adenovirus 0.3%). There were no significant differences between FN episodes with and without viraemia in terms of duration of fever or neutropenia/lymphopenia, severity of mucositis (> II0), incidence of diarrhea and ICU admission. Our results indicate that viraemia in paediatric cancer patients generally does not have a major clinical impact, and may help in the decision regarding the indication of routine evaluation for viraemia in febrile neutropenic, but otherwise asymptomatic children.

Promising immunotherapeutic approaches for primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a large B-cell neoplasm usually presenting as a serious effusion in body cavities without detectable tumor masses. It is an AIDS-related non-Hodgkin's lymphoma (HL) with human herpes virus 8 (HHV8)/Kaposi sarcoma-associated herpes virus (KSHV) infection. A combination antiretroviral therapy (cART) prolongs the lifespan of AIDS and AIDS-related malignant lymphoma patients, but PEL continues to have a dismal prognosis. PEL showed disappointing outcomes with standard chemotherapy such as CHOP or CHOP-like regimens. A PEL status highlights the urgent need for new therapeutic approaches and treatment strategies and improve clinical outcomes. This review discusses the current knowledge and some recent clinical trials for PEL in the platform of immunotherapy as well as promising future immunotherapeutic approaches for PEL.

Microbiological risk factors, ICU survival, and 1-year survival in hematological patients with pneumonia requiring invasive mechanical ventilation

PurposeTo identify pathogenic microorganisms and microbiological risk factors causing high morbidity and mortality in immunocompromised patients requiring invasive mechanical ventilation due to pneumonia.MethodsA retrospective single-center study was performed at the intensive care unit (ICU) of the Department of Internal Medicine at Heidelberg University Hospital (Germany) including 246 consecutive patients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia from 08/2004 to 07/2016. Microbiological and radiological data were collected and statistically analyzed for risk factors for ICU and 1-year mortality.ResultsICU and 1-year mortality were 63.0% (155/246) and 81.0% (196/242), respectively. Pneumonia causing pathogens were identified in 143 (58.1%) patients, multimicrobial infections were present in 51 (20.7%) patients. Fungal, bacterial and viral pathogens were detected in 89 (36.2%), 55 (22.4%) and 41 (16.7%) patients, respectively. Human herpesviruses were concomitantly reactivated in 85 (34.6%) patients. As significant microbiological risk factors for ICU mortality probable invasive Aspergillus disease with positive serum-Galactomannan (odds ratio 3.1 (1.2-8.0), p = 0.021,) and pulmonary Cytomegalovirus reactivation at intubation (odds ratio 5.3 (1.1–26.8), p = 0.043,) were identified. 1-year mortality was not significantly associated with type of infection. Of interest, 19 patients had infections with various respiratory viruses and Aspergillus spp. superinfections and experienced high ICU and 1-year mortality of 78.9% (15/19) and 89.5% (17/19), respectively.ConclusionsPatients with hematological malignancies requiring invasive mechanical ventilation due to pneumonia showed high ICU and 1-year mortality. Pulmonary Aspergillosis and pulmonary reactivation of Cytomegalovirus at intubation were significantly associated with negative outcome.

High-density resolution of the Kaposi's sarcoma associated herpesvirus transcriptome identifies novel transcript isoforms generated by long-range transcription and alternative splicing.

Kaposi's sarcoma-associated herpesvirus is the etiologic agent of Kaposi's sarcoma and two B-cell malignancies. Recent advancements in sequencing technologies have led to high resolution transcriptomes for several human herpesviruses that densely encode genes on both strands. However, for KSHV progress remained limited due to the overall low percentage of KSHV transcripts, even during lytic replication. To address this challenge, we have developed a target enrichment method to increase the KSHV-specific reads for both short- and long-read sequencing platforms. Furthermore, we combined this approach with the Transcriptome Resolution through Integration of Multi-platform Data (TRIMD) pipeline developed previously to annotate transcript structures. TRIMD first builds a scaffold based on long-read sequencing and validates each transcript feature with supporting evidence from Illumina RNA-Seq and deepCAGE sequencing data. Our stringent innovative approach identified 994 unique KSHV transcripts, thus providing the first high-density KSHV lytic transcriptome. We describe a plethora of novel coding and non-coding KSHV transcript isoforms with alternative untranslated regions, splice junctions and open-reading frames, thus providing deeper insights on gene expression regulation of KSHV. Interestingly, as described for Epstein-Barr virus, we identified transcription start sites that augment long-range transcription and may increase the number of latency-associated genes potentially expressed in KS tumors.

Late-onset maple syrup urine disease triggered by human herpesvirus-6 mediated encephalopathy in a toddler

Late-onset maple syrup urine disease triggered by human herpesvirus-6 mediated encephalopathy in a toddler

Fetal cord plasma herpesviruses and preeclampsia: an observational cohort study

A previous study suggested that fetal inheritance of chromosomally integrated human herpesvirus 6 (ici-HHV6) is associated with the hypertensive pregnancy disorder preeclampsia (PE). We aimed to study this question utilizing cord plasma samples (n = 1276) of the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort: 539 from a pregnancy with PE and 737 without. We studied these samples and 30 placentas from PE pregnancies by a multiplex qPCR for the DNAs of all nine human herpesviruses. To assess the population prevalence of iciHHV-6, we studied whole-genome sequencing data from blood-derived DNA of 3421 biobank subjects. Any herpes viral DNA was detected in only two (0.37%) PE and one (0.14%) control sample (OR 2.74, 95% CI 0.25–30.4). One PE sample contained iciHHV-6B and another HHV-7 DNA. The control’s DNA was of iciHHV-6B; the fetus having growth restriction and preterm birth without PE diagnosis. Placentas showed no herpesviruses. In the biobank data, 3 of 3421 subjects (0.08%) had low level HHV-6B but no iciHHV-6. While iciHHV-6 proved extremely rare, both fetuses with iciHHV-6B were growth-restricted, preterm, and from a pregnancy with maternal hypertension. Our findings suggest that human herpesviruses are not a significant cause of PE, whereas iciHHV-6 may pose some fetal risk.

Characterization of Herpesviridae Family Members, BK Virus, and Adenovirus in Children and Adolescents with Nephrotic Syndrome.

A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133-595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children.

Local Power: The Role of Tissue-Resident Immunity in Human Genital Herpes Simplex Virus Reactivation.

From established latency, human herpes virus type 2 (HSV-2) frequently reactivates into the genital tract, resulting in symptomatic ulcers or subclinical shedding. Tissue-resident memory (TRM) CD8+ T cells that accumulate and persist in the genital skin at the local site of recrudescence are the "first responders" to viral reactivation, performing immunosurveillance and containment and aborting the ability of the virus to induce clinical lesions. This review describes the unique spatiotemporal characteristics, transcriptional signatures, and noncatalytic effector functions of TRM CD8+ T cells in the tissue context of human HSV-2 infection. We highlight recent insights into the intricate overlaps between intrinsic resistance, innate defense, and adaptive immunity in the tissue microenvironment and discuss how rapid virus-host dynamics at the skin and mucosal level influence clinical outcomes of genital herpes diseases.

Exploring the Link between Varicella-Zoster Virus, Autoimmune Diseases, and the Role of Recombinant Zoster Vaccine.

The varicella-zoster virus (VZV) is a human neurotropic herpes virus responsible for varicella and herpes zoster (HZ). Following primary infection in childhood, VZV manifests as varicella (chickenpox) and enters a period of latency within the dorsal root ganglion. A compromised cellular immune response due to aging or immunosuppression triggers viral reactivation and the development of HZ (shingles). Patients with autoimmune diseases have a higher risk of developing HZ owing to the immunodeficiency associated with the disease itself and/or the use of immunosuppressive agents. The introduction of new immunosuppressive agents with unique mechanisms has expanded the treatment options for autoimmune diseases but has also increased the risk of HZ. Specifically, Janus kinase (JAK) inhibitors and anifrolumab have raised concerns regarding HZ. Despite treatment advances, a substantial number of patients suffer from complications such as postherpetic neuralgia for prolonged periods. The adjuvanted recombinant zoster vaccine (RZV) is considered safe and effective even in immunocompromised patients. The widespread adoption of RZV may reduce the health and socioeconomic burdens of HZ patients. This review covers the link between VZV and autoimmune diseases, assesses the risk of HZ associated with immunosuppressant use, and discusses the benefits and risks of using RZV in patients with autoimmune diseases.