Oncogenic Infection Research Articles

Monocyte and Macrophage Functions in Oncogenic Viral Infections.

Monocytes and macrophages are part of innate immunity and constitute the first line of defense against pathogens. Bone marrow-derived monocytes circulate in the bloodstream for one to three days and then typically migrate into tissues, where they differentiate into macrophages. Circulatory monocytes represent 5% of the nucleated cells in normal adult blood. Following differentiation, macrophages are distributed into various tissues and organs to take residence and maintain body homeostasis. Emerging evidence has highlighted the critical role of monocytes/macrophages in oncogenic viral infections, mainly their crucial functions in viral persistence and disease progression. These findings open opportunities to target innate immunity in the context of oncogenic viruses and to explore their potential as immunotherapies.

Accelerating Progress to Reduce the Cancer Burden through Prevention and Control in the US.

Improvements in cancer prevention and control are poised to be main contributors in reducing the burden of cancer in the US. We quantify top opportunities to accelerate progress using projected life years gained (LYG) and deaths averted as measures. We project that over the next 25 years, realistic gains from tobacco control can contribute 0.4 to 17 million additional LYG per intervention and 8.4 million additional LYG from improving uptake of screening programs over the lifetime of 25 annual cohorts. Additional opportunities include addressing modifiable risk factors (excess weight, alcohol consumption), improving methods to prevent or treat oncogenic infections, and reducing cancer health disparities. Investment is needed in the pipeline of new preventive agents and technologies for early detection to continue progress. There is also a need for additional research to improve the access to and uptake of existing and emerging interventions for cancer prevention and control and to address health disparities. These gains are undeniably within our power to realize for the US population.

Proportion of cancer cases and deaths attributable to potentially modifiable risk factors in Peru

BackgroundLimited evidence exists on the population attributable fraction (PAF) of cancer cases and deaths in Latin America. In Peru several studies have been published regarding the PAF of various risk factors and their associated diseases. The objective of this study was to estimate the fraction of cancer cases and deaths attributable to potentially modifiable risk factors in Peru in 2018, before the COVID-19 pandemic in the population of 15 years old and older.MethodsAn ecological study was conducted using the prevalence of exposure of the Peruvian population to modifiable risk factors for cancer, the relative risk associated with each factor, and the number of cancer cases and deaths in 2018 as inputs. We used the Parkin formula with a Montecarlo statistical simulation model to calculate the PAF and confidence intervals. The number of new cancer cases and deaths attributed to each risk factor was determined by multiplying the number of cases and deaths in each gender by the PAF of each risk factor.FindingsIn Peru, 38.5% of new cases (34.5% in men and 42% in women) and 43.4% of cancer-related deaths (43.4% in men and 43.4% in women) were attributable to modifiable risk factors. The number of cancers attributable was 25,308 (10,439 in men and 14,869 in women) and the number of deaths attributable to cancer was 14,839 (6,953 in men and 7,886 in women). The predominant modifiable risk factors contributing to the highest number of cases and deaths were HPV infection (4,563 cases, 2,409 deaths), current tobacco use (3,348 cases, 2,180 deaths), and helicobacter pylori infection (2,677 cases, 1,873 deaths). Among the risk factors, oncogenic infections constituted the group with the highest PAF (16.6% for cases, 19.2% for deaths) followed by other unhealthy lifestyle factors (14.2% for cases, 16.7% for deaths), tobacco (7.2% for cases, 7.2% for deaths) and ultraviolet radiation (0.5% for cases, 0.3% for deaths).ConclusionsPrior to the COVID-19 pandemic, 38.5% of cancer cases and 43.4% of cancer-related deaths in Peru were linked to modifiable risk factors in the population of 15 years old and older. Most preventable cancer cases and deaths were related to oncogenic infections, primarily caused by HPV and helicobacter pylori, followed by tobacco and obesity.

Roles of Human Endogenous Retrovirus-K-Encoded Np9 in Human Diseases: A Small Protein with Big Functions.

Human Endogenous Retrovirus Sequences (HERVs) constitute up to 8% of the human genome, yet not all HERVs remain silent passengers within our genomes. Some HERVs, especially HERV type K (HERV-K), have been found to be frequently transactivated in a variety of inflammatory diseases and human cancers. Np9, a small protein translated from the HERV-K env reading frame, has been reported as an oncogenic protein and is present in a variety of tumors and transformed cells. The Np9 protein can crosstalk with many cellular factors and is involved in the pathogenicity of various diseases, including some oncogenic virus infections. In the current review, we summarize recent findings about Np9 clinical relevance/implications, its mediated cellular functions/mechanisms, and potential targeted therapies in development.

Paraneoplastic Syndrome After Kidney Transplantation: Frequency, Risk Factors, Differences to Paraneoplastic Occurrence of Glomerulonephritis in the Native Kidney, and Implications on Long-Term Kidney Graft Function.

Posttransplant malignancies are an important complication of solid organ transplantation. Kidney transplant recipients are at particularly high risk of cancer development. The most relevant risk factors of carcinogenesis are the use of immunosuppressive agents and oncogenic viral infections. Additionally, immune dysregulation caused by these factors may predispose to various types of organ damage. Paraneoplastic glomerular diseases are one of the most interesting and understudied cancer manifestations. The appropriate diagnosis of paraneoplastic glomerular damage can be challenging in kidney transplant recipients, due to factors inherent to concomitant medication and common comorbidities. Recent advances in the field of molecular and clinical nephrology led to a significant improvement in our understanding of glomerular diseases and their more targeted treatment. On the other hand, introduction of novel anticancer drugs tremendously increased patients' survival, at the cost of kidney-related side effects. Our review aims to provide insights into diagnosis and treatment of paraneoplastic glomerular diseases, with a special attention to kidney transplant recipients.

Oncogenic viral antigens for engineered T cell immunotherapy: Challenges and opportunities

AbstractViruses that cause malignancies such as hepatocellular carcinoma and cervical cancer are the cause of approximately 20% of all human cancers. In recent years, engineered T cell immunotherapy targeting tumor‐associated antigens (TAAs) has had some success against virus‐associated cancer, although these treatments are associated with side effects. TAA‐specific‐modified T cells may kill cancer cells but they also react with and damage healthy tissue. During an oncogenic virus infection, viral DNA integrates into the host genome, leading to the expression of viral‐specific antigens in the tumor in a restricted and durable manner. The cross‐reactive side‐effects of conventional TAA‐specific engineered T cell treatment can be avoided by creating engineered T cells that target oncogenic viral antigens. To chart a course for the discovery of additional viral‐specific antigens and their combination with immune checkpoint inhibition therapies, this review summarizes the development, preclinical research, and clinical application of oncogenic viral antigen–specific T cell immunotherapy. This review also addresses challenges such as virus mutation and diverse integration, which can result in the loss of the target.

Molecular and Immunopathological Investigations of Marek’s Disease in HVT Vaccinated Chicken Flocks

Background: The present investigation was carried out on poultry carcasses brought to the Department of Veterinary Pathology, LUVAS, Hisar from Herpesvirus of turkeys (HVT) vaccinated chicken flocks and suspected for viral neoplastic conditions on the basis of necropsy. Conventional and molecular techniques for the confirmation of the Marek’s disease (MD) were studied. For differential diagnosis from other oncogenic viral infections immunohistochemistry as an important tool was investigated. Methods: The conventional diagnosis of MD) was done on basis of clinical signs, gross lesions and histopathology of proliferate lesions; as lymphomatous lesions consist of pleomorphic lymphocytes. For confirmatory diagnosis molecular techniques were employed to detect MD virus specific Meq gene by Taqman probe real time PCR and nested PCR. For differential diagnosis of mixed oncogenic viral infections, immunohistochemistry (IHC) using B and T cell differentiation markers (CD79 alpha and CD3) was employed. Result: Specific Meq gene by Taqman probe real time PCR was positive in 92.5% suspected cases; while nested PCR technique gave positivity in 55% cases. The immunohistochemical reactivity for CD3 gave positive reactivity in the cytoplasm and cell membrane and negative reaction for CD79 alpha in MD positive cases, while in cases with mixed infections of MDV and other viral neoplastic conditions, cells showed positive reactivity to both CD3 and CD79 alpha in neoplastic proliferates.

Rewiring of the Host Cell Metabolome and Lipidome during Lytic Gammaherpesvirus Infection Is Essential for Infectious-Virus Production.

Oncogenic virus infections are estimated to cause ~15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors. IMPORTANCE Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication. We found that MHV-68 infection of host cells increases glucose, glutamine, lipid, and nucleotide metabolic pathways. We also showed inhibition or starvation of glucose, glutamine, or lipid metabolic pathways results in an inhibition of virus production. Ultimately, targeting changes in host cell metabolism due to viral infection can be used to treat gammaherpesvirus-induced cancers and infections in humans.

Second primary cancers in people with HIV/AIDS: a national data linkage study of incidence and risk factors.

The evidence regarding the characteristics of second primary cancer (SPC) in people living with HIV (PLWHIV) is limited. We performed a national population-based data linkage study to determine the incidence and risk factors for SPC in PLWHIV in Australia between 1982 and 2012. We conducted a probabilistic data linkage study to compare the incidence of SPC over time, defined using HIV treatment eras, for SPCs related to oncogenic viral infection in comparison with non-infection related SPCs. Risk factors considered included age at diagnosis of cancer, sex, HIV exposure modality and CD4+ count. Of 29,383 individuals diagnosed with HIV, 3,123 who developed a first primary cancer were included in the analysis. Among them, 229 cases of SPC were identified across 27,398 person years of follow-up. The most common SPCs were non-Hodgkin lymphomas (n=71, 31%). The incidence of SPC overall did not change over time, however there was an increase in individuals diagnosed with HIV in later eras (p-trend=0.001). The incidence of non-infection related SPC increased over time and was associated with older age (p-trend=0.005) and the acquisition of HIV in later eras (p-trend <0.001). Conversely, the incidence of infection-related SPC decreased (p-trend <0.001), but this was no longer significant after adjustment for age (p-trend=0.14). The risk of SPC in PLWHIV in Australia remains high, with a temporal increase observed in non-infection related cancer, likely due to ageing of the population. Optimal screening and prevention strategies for SPC in PLWHIV are increasingly important.

Malignancies in systemic rheumatic diseases: A mini review.

There is an increased risk of malignancies in patients with many systemic rheumatic diseases, which negatively impact on their quality of life. The risk and types of malignancies can differ by the type of rheumatic diseases. Possible mechanisms linking them are dynamic and complicated, including chronic inflammation and damage in rheumatic disease, inability to clear oncogenic infections, shared etiology and some anti-rheumatic therapies. Although certain disease-modifying anti-rheumatic drugs (DMARDs) have been proved to be potentially carcinogenic, the majority of them were not associated with increased risk of most malignancies in patients with systemic rheumatic diseases.

The Hybrid Capture 2 Results in Correlation with the Pap Test, Sexual Behavior, and Characteristics of Romanian Women.

Human papillomavirus (HPV) infection is the major cause of cervical cancer (CC); hence, it is critical to understand the processes by which HPV infection causes squamous intraepithelial lesions, as well as the proper diagnostic tools. The objective of this study was to establish the correlations between Pap test results and Hybrid Capture 2 (HC2) tests findings. This study included 169 women between the ages of 30 and 64, who presented for consultation in gynecological clinics in both the public and the private sectors. These women reported symptoms, such as abnormal vaginal discharge and genital irritation, as well as early onset of sexual activity, multiple sexual partners, history of other sexually transmitted infections or high-risk sexual partners, immunosuppression, or tobacco smoking. Pap tests and HPV testing, using the HC2 method, were performed for the women enrolled in the study, including data gathered after patients completed questionnaires concerning their sexual behavior. The HC2 method revealed that 66 patients (39.1%) tested positive for high-risk HPV types. Of the patients with positive results, 14 (21.2%) presented Atypical Squamous Cells of Undetermined Significance (ASC-US) compared to 10 (9.7%) patients in the negative group (p = 0.042). Atypical Squamous Cells for which a high-grade lesion cannot be excluded (ASC-H) were identified primarily in women with positive HC2 (6.1%). HR-HPV positivity was substantially more associated with low-grade ASC-US or low-grade squamous intraepithelial lesion (LSIL) and high-grade ASC-H cytology (OR = 2.53; 95% CI: 1.10-5.80, respectively, OR = 14.9; 95%CI: 1.006-34.59). Unmarried women (31.8%; p = 0.004) and women with multiple partners (over four partners, 10.6%; p = 0.03) were more likely to have an HPV infection when compared to married women and those with fewer sexual partners. Understanding the epidemiology of HPV genital infections is essential for developing preventive measures against this infection and CC. Identifying the most prevalent HPV types, and determining the incidence of HPV oncogenic infections, in conjunction with Pap test results and sexual behavior information, can constitute part of an algorithm for the efficient management of cervical intraepithelial lesions.

Suppression of KSHV lytic replication and primary effusion lymphoma by selective RNF5 inhibition.

Primary effusion lymphoma (PEL), a rare aggressive B-cell lymphoma in immunosuppressed patients, is etiologically associated with oncogenic γ-herpesvirus infection. Chemotherapy is commonly used to treat PEL but usually results in poor prognosis and survival; thus, novel therapies and drug development are urgently needed for PEL treatment. Here, we demonstrated that inhibition of Ring finger protein 5 (RNF5), an ER-localized E3 ligase, suppresses multiple cellular pathways and lytic replication of Kaposi sarcoma-associated herpesvirus (KSHV) in PEL cells. RNF5 interacts with and induces Ephrin receptors A3 (EphA3) and EphA4 ubiquitination and degradation. RNF5 inhibition increases the levels of EphA3 and EphA4, thereby reducing ERK and Akt activation and KSHV lytic replication. RNF5 inhibition decreased PEL xenograft tumor growth and downregulated viral gene expression, cell cycle gene expression, and hedgehog signaling in xenograft tumors. Our study suggests that RNF5 plays the critical roles in KSHV lytic infection and tumorigenesis of primary effusion lymphoma.

Психологический стресс и папилломавирусная инфекция. Взаимосвязь и пути решения

Stress is a non-specific response of the body to stimuli that disrupt homeostasis. Stress can suppress the immune function and therefore increase the risk of immunodeficiency disorders, including human papillomavirus (HPV) infection. Stress-induced immunosuppression is especially important for infection-related cancer since damage to cellular immunity can stimulate the development of oncogenic viral infection. A connection was established between psychosocial stress and the development of SILs (squamous intraepithelial lesions) in women (formerly known as ‘cervical intraepithelial neoplasia (CIN)’ in the International Classification of Diseases (ICD-10)). This connection ends with immune response, which, in turn, depends on the duration of exposure to stressors: a shorter duration of stress shifts specific immunity to innate immunity, and chronic stress shifts it from a Th1-type response to a Th2-type response. Against the background of cognitive behavioral therapy, the incidence of severe SILs/CIN is significantly lower than in the absence of psychological treatment. However, the use of adaptive ways of coping with stress does not exclude the need for pathogenetic (antiviral) therapy for HPV infection. One of the most demanded medications in the pharmaceutical market of Russia is inosine pranobex. It is included in the register of antiviral medications used for HPV treatment. It enhances antiviral protection against HPV, slows or stops oncogenesis in the cervix, which together contribute to a rapid virus elimination. Key words: stress, immunosuppression, human papillomavirus infection, SILs/CIN, inosine pranobex

Long-Term Projections of Cancer Incidence and Mortality in Japan and Decomposition Analysis of Changes in Cancer Burden, 2020-2054: An Empirical Validation Approach.

The aim of this study was to project new cancer cases/deaths forward to 2054, and decompose changes in cancer cases/deaths to assess the impact of demographic transitions on cancer burden. We collected data on cancer cases/deaths up to 2019, empirically validated the projection performance of multiple statistical models, and selected optimal models by applying time series cross-validation. We showed an increasing number of new cancer cases but decreasing number of cancer deaths in both genders, with a large burden attributed to population aging. We observed the increasing incidence rates in most cancer sites but reducing rates in some infection-associated cancers, including stomach and liver cancers. Colorectal and lung cancers were projected to remain as leading cancer burdens of both incidence and mortality in Japan over 2020-2054, while prostate and female breast cancers would be the leading incidence burdens among men and women, respectively. Findings from decomposition analysis require more supportive interventions for reducing mortality and improving the quality of life of Japanese elders. We emphasize the important role of governments and policymakers in reforming policies for controlling cancer risk factors, including oncogenic infections. The rapid increase and continued presence of those cancer burdens associated with modifiable risk factors warrant greater efforts in cancer control programs, specifically in enhancing cancer screening and controlling cancer risk factors in Japan.

Cancer statistics for American Indian and Alaska Native individuals, 2022: Including increasing disparities in early onset colorectal cancer.

American Indian and Alaska Native (AIAN) individuals are diverse culturally and geographically but share a high prevalence of chronic illness, largely because of obstacles to high-quality health care. The authors comprehensively examined cancer incidence and mortality among non-Hispanic AIAN individuals, compared with non-Hispanic White individuals for context, using population-based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Overall cancer rates among AIAN individuals were 2% higher than among White individuals for incidence (2014 through 2018, confined to Purchased/Referred Care Delivery Area counties to reduce racial misclassification) but 18% higher for mortality (2015 through 2019). However, disparities varied widely by cancer type and geographic region. For example, breast and prostate cancer mortality rates are 8% and 31% higher, respectively, in AIAN individuals than in White individuals despite lower incidence and the availability of early detection tests for these cancers. The burden among AIAN individuals is highest for infection-related cancers (liver, stomach, and cervix), for kidney cancer, and for colorectal cancer among indigenous Alaskans (91.3 vs. 35.5 cases per 100,000 for White Alaskans), who have the highest rates in the world. Steep increases for early onset colorectal cancer, from 18.8 cases per 100,000 Native Alaskans aged 20-49 years during 1998 through 2002 to 34.8 cases per 100,000 during 2014 through 2018, exacerbated this disparity. Death rates for infection-related cancers (liver, stomach, and cervix), as well as kidney cancer, were approximately two-fold higher among AIAN individuals compared with White individuals. These findings highlight the need for more effective strategies to reduce the prevalence of chronic oncogenic infections and improve access to high-quality cancer screening and treatment for AIAN individuals. Mitigating the disparate burden will require expanded financial support of tribal health care as well as increased collaboration and engagement with this marginalized population.

Photodynamic Therapy: A Prospective Therapeutic Approach for Viral Infections and Induced Neoplasia.

The recent COVID-19 pandemic outbreak and arising complications during treatments have highlighted and demonstrated again the evolving ability of microorganisms, especially viral resistance to treatment as they develop into new and strong strains. The search for novel and effective treatments to counter the effects of ever-changing viruses is undergoing. Although it is an approved procedure for treating cancer, photodynamic therapy (PDT) was first used against bacteria and has now shown potential against viruses and certain induced diseases. PDT is a multi-stage process and uses photosensitizing molecules (PSs) that accumulate in diseased tissues and eradicates them after being light-activated in the presence of oxygen. In this review, studies describing viruses and their roles in disrupting cell regulation mechanisms and signaling pathways and facilitating tumorigenesis were described. With the development of innovative “or smart” PSs through the use of nanoparticles and two-photon excitation, among other strategies, PDT can boost immune responses, inactivate viral infections, and eradicate neoplastic cells. Visualization and monitoring of biological processes can be achieved in real-time with nanomedicines and better tissue penetration strategies. After photodynamic inactivation of viruses, signaling pathways seem to be restored but the underlying mechanisms are still to be elucidated. Light-mediated treatments are suitable to manage both oncogenic viral infections and induced neoplasia.

Oncogenic viruses, cancer biology, and innate immunity.

Malignancies that arise as a result of viral infection account for roughly 15% of cancer cases worldwide. The innate immune system is the body's first line of defense against oncogenic viral infection and is also involved in the response against viral-driven tumors. In this review, we discuss research advances made over the last five years elucidating how the innate immune system recognizes and responds to oncogenic viruses, how these viruses have evolved to escape this immune pressure, and ways that innate immunity can inform the development of novel therapeutics against oncogenic viral infection and their associated cancers.

S1389 The Impact of Race on the Overall Survival Rate of Hepatocellular Carcinoma in the African-American Population

Introduction: Hepatocellular carcinoma (HCC) accounts for approximately 90% of the incidence of all primary liver cancers. It is also the fifth most prevalent malignancy worldwide and the fourth global leading cause of death. Previous U.S.-based studies on survival rates suggest ethnic disparities among HCC patients; however, this is incompletely understood due to a variety of risk factors. Notable risk factors include oncogenic viral infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), alcohol abuse, and metabolic syndrome secondary to obesity and diabetes mellitus. This study aims to investigate whether race plays a role in the overall survival rate of hepatocellular carcinoma. Methods: Using the cBioPortal platform and systematic bioinformatical-analysis of The Cancer Genome Atlas (TCGA) PanCancer Atlas dataset, we analyzed the effect of race on overall survival rate. The study included 360 HCC patients (234 living patients and 126 deceased patients). The following races were included: White, Black or African American, and Asian. Results: The impact of race on the overall survival rate of hepatocellular carcinoma was statistically significant (p < 0.0206) and appeared to be higher in the African American group (64.71%) compared to the White (57.92%). Of note, the Asian group had the highest overall survival rate (73.13%). (Figure) Conclusion: The findings in this study suggest that race may play a role in the risk of developing hepatocellular carcinoma and potential treatment options. Further studies are warranted to evaluate the genetic alterations in various race groups.Figure 1.: Hepatocellular carcinoma overall survival among the African American, White, and Asian populations.

Malignancies in adult kidney transplant candidates and recipients: current status.

Posttransplant malignancies, particularly recurrent and de novo, in solid organs including kidney transplant recipients (KTRs) are a significant complication associated with substantial mortality, largely attributed to the long-term immunosuppression necessary to maintain allograft tolerance. Older age at transplantation and oncogenic virus infection along with pretransplant malignancies are among the main factors contributing to the risk of cancer in this population. As the mean age of transplant candidates rises, the rate of transplant recipients with pretransplant malignancies also increases. The eligibility criteria for transplantation in patients with prior cancer have recently changed. The overall risk of posttransplant malignancies is at least double after transplantation, including KTRs, relative to the general population, and is most pronounced for skin cancers associated with UV radiation and virally mediated tumors. The risk of renal cell carcinoma is specifically increased in the kidney transplant population. The therapy for cancer in transplant patients is associated with risk of higher toxicity, and graft rejection and/or impairment, which poses a unique challenge in its management. Reduction of immunosuppression and the use of mammalian target of rapamycin inhibitors are common after cancer diagnosis, although optimal immunosuppression for transplant recipients with cancer remains undefined. Suboptimal cancer treatment contributing to a worse prognosis has been reported for malignancies in this population. In this article, we focus on the prevalence and outcomes of posttransplant malignancies, cancer therapy including a short overview of immunotherapy, cancer screening and prevention strategies, and immunosuppression as a cancer risk factor. The 2020/2021 recommendations of the Kidney Disease: Improving Global Outcomes and the American Society of Transplantation for transplant candidates with a history of cancer are presented.

Time-resolved transcriptomes reveal diverse B cell fate trajectories in the early response to Epstein-Barr virus infection.

Epstein-Barr virus infection of B lymphocytes elicits diverse host responses via well-adapted transcriptional control dynamics. Consequently, this host-pathogen interaction provides a powerful system to explore fundamental processes leading to consensus fate decisions. Here, we use single-cell transcriptomics to construct a genome-wide multistate model of B cell fates upon EBV infection. Additional single-cell data from human tonsils reveal correspondence of model states to analogous invivo phenotypes within secondary lymphoid tissue, including an EBV+ analog of multipotent activated precursors that can yield early memory B cells. These resources yield exquisitely detailed perspectives of the transforming cellular landscape during an oncogenic viral infection that simulates antigen-induced B cell activation and differentiation. Thus, they support investigations of state-specific EBV-host dynamics, effector B cell fates, and lymphomagenesis. To demonstrate this potential, we identify EBV infection dynamics in FCRL4+/TBX21+ atypical memory B cells that are pathogenically associated with numerous immune disorders.