Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection.

Although pathologies associated with acute virus infections have been extensively studied, the effects of long-term latent virus infections are less well understood. Human cytomegalovirus, which infects 50% to 80% of humans, is usually acquired during early life and persists in a latent state for the lifetime. The purpose of this study was to determine whether systemic murine cytomegalovirus (MCMV) infection acquired early in life disseminates to and becomes latent in the eye and if ocular MCMV can trigger in situ inflammation and occurrence of ocular pathology. This study found that neonatal infection of BALB/c mice with MCMV resulted in dissemination of virus to the eye, where it localized principally to choroidal endothelia and pericytes and less frequently to the retinal pigment epithelium (RPE) cells. MCMV underwent ocular latency, which was associated with expression of multiple virus genes and from which MCMV could be reactivated by immunosuppression. Latent ocular infection was associated with significant up-regulation of several inflammatory/angiogenic factors. Retinal and choroidal pathologies developed in a progressive manner, with deposits appearing at both basal and apical aspects of the RPE, RPE/choroidal atrophy, photoreceptor degeneration, and neovascularization. The pathologies induced by long-term ocular MCMV latency share features of previously described human ocular diseases, such as age-related macular degeneration.

Viral Infections in Burns.

Background: Viral infections after burns are less common than bacterial infections but usually occur in the more severely burned patients and have been associated with poor outcomes. Methods: Retrospective reviews and case series were examined to provide an overview of the management of viral infections in the burn patient. Results: The most common viral pathogens in these patients are the herpesviruses, which include herpes simplex, varicella zoster, cytomegalovirus, and human herpesvirus 6. Established viral infections that may complicate patient management include human immunodeficiency virus, hepatitis B and C, and, more recently, the novel coronavirus SARS-CoV-2. Herpesvirus infections can occur as primary or nosocomial pathogens but clinical manifestations most commonly are re-activation of latent viral infection. Because of the paucity of data in the burn population, much of the evidence for specific treatments is extrapolated from patients with severe immunosuppression or critical illness. Antiviral therapy is employed for the burn patient with herpesvirus infections. This is an area of active study, and further research is needed to better understand the risks, clinical manifestations, and attributable morbidity and mortality of viral infections. Conclusions: Major burn injury results in immunosuppression and viral infection in a small number of patients. Recognition and antiviral therapy are employed, but additional studies are necessary to improve outcomes in these patients.

Improved automatic detection of herpesvirus secondary envelopment stages in electron microscopy by augmenting training data with synthetic labelled images generated by a generative adversarial network.

Detailed analysis of secondary envelopment of the herpesvirus human cytomegalovirus (HCMV) by transmission electron microscopy (TEM) is crucial for understanding the formation of infectious virions. Here, we present a convolutional neural network (CNN) that automatically recognises cytoplasmic capsids and distinguishes between three HCMV capsid envelopment stages in TEM images. 315 TEM images containing 2,610 expert-labelled capsids of the three classes were available for CNN training. To overcome the limitation of small training datasets and thus poor CNN performance, we used a deep learning method, the generative adversarial network (GAN), to automatically increase our labelled training dataset with 500 synthetic images and thus to 9,192 labelled capsids. The synthetic TEM images were added to the ground truth dataset to train the Faster R-CNN deep learning-based object detector. Training with 315 ground truth images yielded an average precision (AP) of 53.81% for detection, whereas the addition of 500 synthetic training images increased the AP to 76.48%. This shows that generation and additional use of synthetic labelled images for detector training is an inexpensive way to improve detector performance. This work combines the gold standard of secondary envelopment research with state-of-the-art deep learning technology to speed up automatic image analysis even when large labelled training datasets are not available.

Brentuximab vedotin as frontline treatment for HIV-related extracavitary primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare and aggressive herpesvirus-8 (HHV-8) driven B cell non-Hodgkin's lymphoma (NHL) that is usually associated with human immunodeficiency virus (HIV) infection, and has a poor prognosis. PEL is comprised of two clinically distinct but pathologically similar variants: classic and extracavitary PEL. Based on retrospective series, treatment options include combined antiretroviral therapy (cART) in conjunction with chemotherapy regimens used in other forms of NHLs. Treatment outcomes with this approach are usually dismal and there is no standard of care. We present a case of a patient with HIV associated CD30+ extracavitary PEL unfit for multi-agent chemotherapy, who achieved a durable complete response with single agent brentuximab-vedotin and cART.

Herpesvirus Infections of the Nervous System.

PURPOSE OF REVIEW: This article reviews the spectrum of neurologic disease associated with human herpesvirus infections. RECENT FINDINGS: As more patients are becoming therapeutically immunosuppressed, human herpesvirus infections are increasingly common. Historically, infections with human herpesviruses were described as temporal lobe encephalitis caused by herpes simplex virus type 1 or type 2. More recently, however, additional pathogens, such as varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 have been identified to cause serious neurologic infections. As literature emerges, clinical presentations of herpesvirus infections have taken on many new forms, becoming heterogeneous and involving nearly every location along the neuraxis. Advanced diagnostic methods are now available for each specific pathogen in the herpesvirus family. As data emerge on viral resistance to conventional therapies, newer antiviral medications must be considered. SUMMARY: Infections from the herpesvirus family can have devastating neurologic outcomes without prompt and appropriate treatment. Clinical recognition of symptoms and appropriate advanced testing are necessary to correctly identify the infectious etiology. Knowledge of secondary neurologic complications of disease is equally important to prevent additional morbidity and mortality. This article discusses infections of the central and peripheral nervous systems caused by herpes simplex virus type 1 and type 2, varicella-zoster virus, Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6. The pathophysiology, epidemiology, clinical presentations of disease, diagnostic investigations, imaging characteristics, and treatment for each infectious etiology are discussed in detail.

Neurological Disorders Associated with Human Alphaherpesviruses.

Herpes simplex virus (HSV) encephalitis is the most common cause of sporadic fatal encephalitis worldwide, and central nervous system (CNS) involvement is observed in approximately one-third of neonatal HSV infections . In recent years, single-gene inborn errors of innate immunity have been shown to be associated with susceptibility to HSV encephalitis . Temporal lobe abnormalities revealed by magnetic resonance imaging-the most sensitive imaging method for HSV encephalitis-are considered strong evidence for the disease. Detection of HSV DNA in the cerebrospinal fluid by polymerase chain reaction (PCR) is the gold standard for the diagnosis of HSV encephalitis and neonatal meningoencephalitis. Intravenous acyclovir for 14-21 days is the standard treatment in HSV encephalitis. Neurological outcomes in neonates are improved by intravenous high-dose acyclovir for 21 days followed by oral acyclovir suppressive therapy for 6 months. Varicella-zoster virus (VZV) causes a wide range of CNS manifestations. VZV encephalitis typically occurs after primary infection, and reactivation of VZV may cause encephalitis. On the other hand, VZV infection of cerebral arteries produces vasculopathy, which can manifest as ischemic stroke. Vasculopathy can occur after primary infection or reactivation of VZV. PCR detection of VZV DNA in the cerebrospinal fluid can be used for the diagnosis of encephalitis or vasculopathy. Although there are no controlled treatment trials to assess VZV treatments of encephalitis or vasculopathy, intravenous acyclovir is a common treatment.

Factors Leading to Oro-Facial Herpetic Eruptions in Patients Undergoing Surgery for Vestibular Schwannoma.

OBJECTIVE: To study factors influencing oro-facial herpetic eruptions (HEs) in patients undergoing retromastoid suboccipital craniectomy for vestibular schwannomas (VS). METHODS: A retrospective analysis of the prospectively collected database (from July 2014 to December 2015). A total of 87 patients underwent retromastoid suboccipital craniectomy for VS at our center. For the purpose of analysis the patient subset was divided into 2 groups, HE and non-HE. Pearson χ2 test or Fisher exact test were used to identify the factors. RESULTS: The overall incidence of postoperative HE was less than 1% (0.89%, 26 patients of 2916 cases); whereas after VS surgery, it was 20.69% (18 of 87). Demographic profiles of patients in the 2 groups were comparable. Average tumor size (with HE 3.19 ± 2 × 0.67 cm, non-HE 3.38 ± 2 × 1.07 cm), consistency, and laterality also were comparable between the 2 groups. Factors favoring development of postoperative HEs were large size (12 vs. 22, P = 0.013) and preoperative trigeminal nerve (CN V) involvement (9 of 18, 50%, P = 0.046). All patients developed HE in maxillary division of trigeminal nerve (V2), whereas involvement of ophthalmic (V1) and mandibular (V3) divisions were involved less commonly in combination with V2 (V2, 72.2%; V2 + V3, 22.2%; V1 + V2 + V3, 5.6%). The majority of the patients (55.56%) developed HE on postoperative day 3 and none beyond postoperative day 5. All patients responded to empirical oral acyclovir. CONCLUSIONS: The study highlights the relatively high incidence and factors associated with this rare but benign complication.

High-Resolution Vessel Wall Magnetic Resonance Imaging in Varicella-Zoster Virus Vasculitis.

Varicella-zoster virus vasculopathy is a rare but potentially treatable condition. Diagnosis has been based on angiography, brain magnetic resonance imaging (MRI), and cerebrospinal fluid analysis. High-resolution vessel wall MRI may aid to the diagnosis by differentiating inflammation from other vessel wall pathologies. We present the characteristic MRI findings of this condition in a young patient presenting with ischemic stroke.

[Arguments for an infectious cause of IUGR]. / Quels arguments pour déterminer l'origine infectieuse d'un retard de croissance intra-utérin?

Intra-uterine growth retardation (IUGR) is a frequent cause of consultation in antenatal care unit. The prognosis relies on the etiology: vascular, chromosomic, genetic, or infectious. Because of chronic fetal distress, hypotrophy increase morbidity, mortality and neurosensorial long term effect. Usually, infection is involved in 5 to 15% of the IUGR, mainly by Cytomegalovirus (CMV), Varicella Zoster virus, rubella, toxoplasmosis, herpes and syphilis. Maternal sera and amniotic liquid analysis make the diagnosis possible but fetal ultrasound scan is used to find other features. Most of the abnormalities are unspecific but their combination can worsen fetal prognosis. Infection should always be ruled out in the assessment of IUGR.

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings in a patient with human immunodeficiency virus-associated Castleman's disease and Kaposi sarcoma, disorders associated with human herpes virus 8 infection.

We report a case of a 38-year-old man affected by the human immunodeficiency virus (HIV) with a diagnosis of Castleman's disease, plasmablastic type human herpes virus 8 infection, and Kaposi sarcoma based on a histological examination of one cervical lymph node biopsy. The patient underwent (18)F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT). (18)F-FDG-PET/ CT seems to be a valuable tool in patients with HIV-associated Castleman's disease and Kaposi sarcoma. It allows accurate staging and identifies more sites of disease than conventional CT.

Survival of a cat with pneumonia due to cowpox virus and feline herpesvirus infection.

Cowpox virus infection in cats is rare and usually leads to cutaneous lesions alone. Pulmonary infection and pneumonia have been documented occasionally but all such cases described to date have been fatal. Although usually affecting the upper respiratory tract, feline herpesvirus can also induce pneumonia. The present report describes the case of a cat that recovered from a pneumonia in which both poxvirus and feline herpesvirus were demonstrated.

Imaging virus-associated cancer.

Cancer remains an important and growing health problem. Researchers have made great progress in defining genetic and molecular alterations that contribute to cancer formation and progression. Molecular imaging can identify appropriate patients for targeted cancer therapy and may detect early biochemical changes in tumors during therapy, some of which may have important prognostic implications. Progress in this field continues largely due to a union between molecular genetics and advanced imaging technology. This review details uses of molecular-genetic imaging in the context of tumor-associated viruses. Under certain conditions, and particularly during pharmacologic stimulation, gammaherpesviruses will express genes that enable imaging and therapy in vivo. The techniques discussed are readily translatable to the clinic.

Role of HIV and human herpesvirus-8 infection in pulmonary arterial hypertension.

BACKGROUND: Previous work has found a high prevalence of pulmonary arterial hypertension in HIV-infected persons, but establishment of a causal relationship has been limited by the lack of well characterized contemporaneous HIV-uninfected comparator groups. Among HIV-uninfected persons, human herpesvirus-8 (HHV-8) has also been linked to pulmonary arterial hypertension (PAH), but whether this relationship occurs among HIV-infected persons - who have among the highest prevalence of HHV-8 infection - has not been examined. METHODS AND RESULTS: We echocardiographically calculated pulmonary artery systolic pressure and measured HHV-8 antibodies in HIV-infected and HIV-uninfected adults. Among the 196 HIV-infected participants, the median pulmonary artery systolic pressure (PASP) was 27.5 mmHg and 35.2% had PASP greater than 30 mmHg. This compared to a median of 22 mmHg among 52 HIV-uninfected participants in whom 7.7% had a PASP greater than 30 mmHg (P < 0.001). After adjustment for injecting drug and stimulant use, smoking, age, and gender, HIV-infected participants had 5.1 mmHg higher mean PASP and seven fold greater odds of having a PASP greater than 30 mmHg (P < 0.001). Although we found no association between HHV-8 and PAH among all HIV-infected participants, a borderline relationship was present when restricting to those without risk factors for PAH. CONCLUSION: HIV-infected persons have a high prevalence of elevated PASP, which is independent of other risk factors for PAH. This suggests a causal role of HIV in PAH and emphasizes the need to understand the natural history of PAH in this setting. A role for HHV-8 infection in PAH remains much less definitive.

Viral pneumonias in adults: radiologic and pathologic findings.

Numerous viruses, including influenza virus, measles virus, Hantavirus, adenovirus, herpesviruses, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus, can cause lower respiratory tract infection in adults. Viral pneumonia in adults can be classified into two clinical groups: so-called atypical pneumonia in otherwise healthy hosts and viral pneumonia in immunocompromised hosts. Influenza virus types A and B cause most cases of viral pneumonia in immunocompetent adults. Immunocompromised hosts are susceptible to pneumonias caused by cytomegalovirus, herpesviruses, measles virus, and adenovirus. The radiographic findings, which consist mainly of patchy or diffuse ground-glass opacity with or without consolidation and reticular areas of increased opacity, are variable and overlapping. Computed tomographic findings, which are also overlapping, consist of poorly defined centrilobular nodules, ground-glass attenuation with a lobular distribution, segmental consolidation, or diffuse ground-glass attenuation with thickened interlobular septa. The radiologic findings reflect the variable extents of the histopathologic features: diffuse alveolar damage (intraalveolar edema, fibrin, and variable cellular infiltrates with a hyaline membrane), intraalveolar hemorrhage, and interstitial (intrapulmonary or airway) inflammatory cell infiltration. Clinical information such as patient age, immune status, community outbreaks, symptom onset and duration, and presence of a rash remain important aids in diagnosis of viral causes.

Kaposi's sarcoma-associated herpesvirus infection in the lung in multicentric Castleman's disease.

A 32-year-old female was admitted for evaluation of multiple infiltrates on a chest radiograph. A diagnosis of multicentric Castleman's disease was made on the basis of typical clinical manifestations. Transbronchial lung biopsy (TBLB) revealed histological findings reported in lymphocytic interstitial pneumonia. Both the polymerase chain reaction and in situ hybridization with a probe specific for Kaposi's sarcoma-associated herpesvirus (KSHV) sequences demonstrated the presence of KSHV in the TBLB sample.

Cellular localization of human herpesvirus 8 in nonneoplastic lymphadenopathies and chronic interstitial pneumonitis by in situ polymerase chain reaction studies.

OBJECTIVES: To study the cellular localization of human herpesvirus 8 (HHV-8) in rare cases of HHV-8 infection from Italy that are associated neither with human immunodeficiency virus (HIV) infection nor Kaposi's sarcoma (KS). METHODS: The presence and distribution of HHV-8-infected cells was investigated by direct in situ polymerase chain reaction (PCR) in the lymph node tissues from 2 patients with reactive lymphadenopathies with florid follicular hyperplasia and increased vascularity and in the lung tissue from 1 patient with chronic interstitial pneumonitis. RESULTS: HHV-8 was localized in lymphoid and monocyte-macrophage cells scattered in the interfollicular regions of both lymph nodes but not in endothelial cells. In the lung tissue, HHV-8 was found in the inflammatory cells infiltrating the interalveolar interstitium, in endothelial cells of the pulmonary vasculature, and in rare pneumocytes. CONCLUSIONS: HHV-8 can infect nonneoplastic lymph nodes of immunocompetent subjects, and the distribution of infected cells outside of the germinal centers resembles that of Epstein-Barr virus (EBV)-infected cells in the lymph nodes in the course of infectious mononucleosis. Endothelial cells and pneumocytes may be a target of HHV-8 infection out of the KS setting, at least in the presence of a chronic inflammatory process.

Association of body cavity-based lymphoma and human herpesvirus 8 in an HIV-seronegative male. Report of a case with immunocytochemical and molecular studies.

BACKGROUND: Recently lymphomas arising primarily in serosal surfaces have been found in patients with advanced acquired immunodeficiency syndrome (AIDS), but they very rarely seem to occur in human immunodeficiency virus (HIV)-negative patients. Studies on a subset of these lymphomas suggested that they represent a distinct entity associated with Kaposi's sarcoma-associated herpesvirus or human herpesvirus 8 (HHV-8). CASE: An 83-year-old, HIV-negative male was admitted to the hospital with a massive pleural effusion. Abdominal and chest computed tomographic scanning was normal. Cytologic analysis of the pleural effusion revealed a large cell, non-Hodgkin's lymphoma. Polymerase chain reaction analyses on genomic DNA from the pleural effusion demonstrated the presence of HHV-8 sequences in the absence of Epstein-Barr virus. CONCLUSION: It is possible and advantageous to diagnose body cavity-based lymphoma with a combination of cytologic, immunocytochemical and molecular studies of the pleural effusion in conjunction with clinical and radiographic information.