Challenging the Conventional Interpretation of HCMV Seronegativity

The majority of adults in the world (around 83%) carry antibodies reactive with HCMV and are thought to retain inactive or latent infections lifelong. The virus is transmitted via saliva, so infection events are likely to be common. Indeed, it is hard to imagine a life without exposure to HCMV. From 45 seronegative individuals (13 renal transplant recipients, 32 healthy adults), we present seven cases who had detectable HCMV DNA in their blood and/or saliva, or a CMV-encoded homologue of IL-10 (vIL-10) in their plasma. One case displayed NK cells characteristic of CMV infection before her HCMV DNA became undetectable. In other cases, the infection may persist with seroconversion blocked by vIL-10. Future research should seek mechanisms that can prevent an individual from seroconverting despite a persistent HCMV infection, as HCMV vaccines may not work well in such people.

A hyper-immunogenic and slow-growing fungal strain induces a murine granulomatous response to cryptococcal infection

Many successful pathogens cause latent infections, remaining dormant within the host for years but retaining the ability to reactivate to cause symptomatic disease. The human opportunistic pathogen Cryptococcus neoformans is a ubiquitous yeast that establishes latent pulmonary infections in immunocompetent individuals upon fungal inhalation from the environment. These latent infections are frequently characterized by granulomas, or foci of chronic inflammation, that contain dormant cryptococcal cells. Immunosuppression causes these granulomas to break down and release viable fungal cells that proliferate, disseminate, and eventually cause lethal cryptococcosis. This course of C. neoformans dormancy and reactivation is understudied due to limited models, as chronic pulmonary granulomas do not typically form in most mouse models of cryptococcal infection. Here, we report that a previously characterized Cryptococcus-specific gene which is required for host-induced cell wall remodeling, MAR1, inhibits murine granuloma formation. Specifically, the mar1Δ loss-of-function mutant strain induces mature pulmonary granulomas at sites of infection dormancy in mice. Our data suggest that the combination of reduced fungal burden and increased immunogenicity of the mar1Δ mutant strain stimulates a host immune response that contains viable fungi within granulomas. Furthermore, we find that the mar1Δ mutant strain has slow growth and hypoxia resistance phenotypes, which may enable fungal persistence within pulmonary granulomas. Together with the conventional primary murine infection model, latent murine infection models will advance our understanding of cryptococcal disease progression and define fungal features important for persistence in the human host.

What is the risk of a deadly adenovirus pandemic?

Many of us had refresher courses in virology, immunology, and epidemiology in 2020, and we were reminded of the fact that Homo sapiens, the wiliest predator on the planet, has been hunting everything that moves for millennia. These repeated interspecies contacts inherently lead to recurrent zoonosis (nonhuman to human) and anthroponosis (human to nonhuman). Given the accelerating changes in our ecosystems since the neolithic revolution, it was not surprising to see a virus that spreads via aerosolization and liquid droplets cause a pandemic in a few months. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic begs the question—which viruses could cause a global threat? In this Opinion, the characteristics that make adenoviruses a risk, which include efficient intra- and interspecies transmission, thermostable particles, persistent/latent infections in diverse hosts, and the ability to readily recombine and escape herd immunity, are discussed.

Challenging the Conventional Interpretation of HCMV Seronegativity

The majority of adults in the world (around 83%) carry antibodies reactive with HCMV and are thought to retain inactive or latent infections lifelong. The virus is transmitted via saliva so infection events are likely to be common. Indeed it is hard to imagine a life without exposure to HCMV. From 45 seronegative individuals (13 renal transplant recipients, 32 healthy adults), we present seven cases who had detectable HCMV DNA in their blood and/or saliva, or a CMV-encoded homologue of IL-10 (vIL-10) in their plasma. One case displayed NK cells characteristic of CMV infection, and HCMV DNA became undetectable. In other cases, the infection may persist with seroconversion blocked by vIL-10. Future research should seek mechanisms that can prevent an individual from seroconverting despite a persistent HCMV infection, as HCMV vaccines may not work well in such people.

Puccinia buxi.

P. buxi is an autoecious microcyclic rust, completing its life cycle with two spore forms on one host. It is native to parts of Europe and Asia. An introduction to the USA, is evidence that it can be invasive with respect to other temperate countries, particularly because its hosts in the genus Buxus are often propagated vegetatively and may carry latent infections. Boxwoods have long been popular as ornamentals, therefore the rust's current absence from North America and temperate regions of the southern hemisphere is puzzling; in the earliest introductions of the host, the pathogen would probably have been ignored or overlooked. Conditions of boxwood cultivation may discourage the rust's growth and survival.

Proportion of new genital human papillomavirus detections attributable to latent infections: Implications for cervical cancer screening

Background: Infections with human papillomaviruses (HPV) may enter into a latent state in epithelial basal cells, and eventually become reactivated following loss of immune control. It is unclear what proportion of incident detections of HPV are due to reactivation of previous latent infections versus new transmissions. Methods: The HITCH cohort study prospectively followed young newly formed heterosexual partners recruited between 2005-2011 in Montreal, Canada. We calculated the fraction of incident HPV detections non-attributable to sexual transmission risk factors with a Bayesian Markov state transition model. Results are the median (2.5-95.5th percentiles) of the estimated posterior distribution. Findings: 544 type-specific incident HPV detection events occurred in 849 participants; 32.5% of all incident HPV detections occurred in participants whose HITCH partners were negative for that HPV type and who did not report having sex with anyone else over follow-up. We estimate that 42.7% (38.4-47.2%) of all incident HPV detections in this population might be attributable to reactivation of latent infections, not transmission. Interpretation: A positive HPV test result in many cases may be a reactivated past infection, rather than a new infection from recent sexual behaviors or partner infidelity. The potential for reactivation of latent infections in previously HPV-negative women should be considered in the context of cervical cancer screening.

Occurrence of Canker and Wood Rot Pathogens on Stone Fruit Propagation Material and Nursery Trees in the Western Cape of South Africa

Dieback and canker of young stone fruit trees can cause suboptimal growth and even death under severe conditions. One source of inoculum of canker pathogens could be through nursery trees harboring latent infections that would not be visible to inspections done according to the deciduous fruit scheme. The objectives of this study were to identify the canker and wood rot fungal pathogens present in nursery stone fruit trees as well as propagation material and to evaluate their pathogenicity. Isolations were made from scion and rootstock propagation material and from certified nursery stone fruit trees. The plant material sampled did not have any external symptoms. The certified nursery trees when cross-sectioned displayed brown discoloration from the pruning wound, bud union and often from the crown. Fungal species isolated were identified by sequencing of the relevant barcoding genes and phylogenetic analyses thereof. Canker and wood rot associated fungi were identified. Buds used for budding had low levels of infection, with 1.2% of dormant buds infected and 0.4% of green buds infected. The dormant rootstock shoots had canker pathogen incidence of 6.2% before it was planted in the nursery fields and increased as the ungrafted, rooted rootstock plants had 11.1% infection with canker and wood rot pathogens. Out of 1080 nursery trees, the canker and wood rot associated fungi infected 21.8% of trees. The canker causing pathogens that were isolated the most were Cadophora luteo-olivacea and Diplodia seriata. A low incidence of wood rot fungi was found with only 1.5% of nursery trees infected. In total 26 new reports of fungal species on stone fruit in South Africa were made. Of these, 22 have not been found on stone fruit world-wide. The pathogenicity trials’ results confirmed the pathogenic status of these newly reported species. All of the isolates tested formed lesions significantly longer than the control, 4 months after wound inoculation of 2-year-old shoots of two plum orchards. Lasiodiplodia theobromae was the most virulent species on both plum cultivars. The results of this research showed that nursery stone fruit trees and propagation material can harbor latent infections. Different management practices need to be evaluated to prevent these infections to ensure healthier stone fruit nursery trees.

Limited Evidence for Accumulation of Latent Infections of Canker-Causing Pathogens in Shoots of Stone Fruit and Nut Crops in California

Prevalence of latent infections of the canker-causing fungi Botryosphaeria dothidea and species of Cytospora, Diplodia, Lasiodiplodia, Neofusicoccum, and Phomopsis in young shoots of almond, prune and walnut trees in California was studied to test the hypotheses that 1) latent infections accumulate from current-season shoots to 1-year-old shoots in the orchard and 2) there are distinct associations among pathogen taxa present as latent infections in the same shoot. Samples of newly-emerged and 1-year-old shoots were periodically collected in each almond, prune, and walnut orchard for two growing seasons. A real-time quantitative PCR assay was used to quantify latent infection with three parameters: incidence, molecular severity and latent infection index. Diplodia spp. were absent from most samples. For almond, Lasiodiplodia spp. and Cytospora spp. were detected with a maximum incidence >90%, while B. dothidea and Neofusicoccumspp. incidence was <20% in most cases. In prune orchards, the incidence levels of B. dothidea were >50% in most cases, while those of Cytospora spp. and Lasiodiplodia spp. were 30 - 60% and 30 - 100%, respectively. For walnut, many samplings showed higher incidence in 1-year-old (30 – 80%) than in newly-emerged shoots (10 – 50%). Accumulation of latent infection between the two shoot age classes was detected in only few cases. The percentages of samples showing coexistence of two, three and four pathogen taxa in the same shoot were 20 – 25%, <10% and <5%, respectively. Pairwise associations among pathogen taxa in the same shoot were significant in many cases.

Latent Toxoplasma gondii infections are associated with elevated biomarkers of inflammation and vascular injury

Background Toxoplasma gondii is a protozoan parasite that infects cats as definitive hosts and other warm-blooded animals including humans as intermediate hosts. It forms infectious cysts in the brain, muscle and other tissues establishing life-long latent infection. Approximately 10% of the US population is infected. While latent infections are largely asymptomatic, they are associated with neurological deficits and elevated risks of neuropsychiatric diseases. Methods This cross-sectional epidemiological study investigated associations of T. gondii infections with biomarkers of inflammation and vascular injury: soluble intercellular adhesion molecule 1 (ICAM-1), soluble vascular cell adhesion molecule 1 (VCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Serum samples from 694 adults in the Raleigh-Durham-Chapel Hill, North Carolina metropolitan area were tested for IgG antibody response to T. gondii, and for the above biomarkers using commercially available assays. Results T. gondii seroprevalence rate in this sample was 9.7%. Seropositivity was significantly associated with 11% (95% confidence limits 4, 20%) greater median levels of VCAM-1 (p = 0.003), and marginally significantly with 9% (1, 17%), and 36% (1, 83%) greater median levels of ICAM-1, and CRP, respectively (p = 0.04 for each) after adjusting for sociodemographic and behavioral covariates, while the 23% (− 7, 64%) adjusted effect on SAA was not statistically significant (p = 0.15). Conclusions Latent infections with T. gondii are associated with elevated biomarkers of chronic inflammation and vascular injury that are also known to be affected by ambient air pollution.