Silent Virus Research Articles

Integrated Strategies for Aedes aegypti Control Applied to Individual Houses: An Approach to Mitigate Vectorial Arbovirus Transmission.

Aedes aegypti and Culex quinquefasciatus mosquitoes are vectors of different arboviruses that cause a large burden of disease in humans worldwide. A key step towards reducing the impact of arboviruses on humans can be achieved through integrated mosquito surveillance and control approaches. We carried out an integrated approach of mosquito surveillance and control actions to reduce populations of these insects along with a viral surveillance in a neighborhood of Recife (Northeastern Brazil) with high mosquito densities and arbovirus transmission. The actions were carried out in 40 different houses in the Nova Descoberta neighborhood. The area was divided into two groups, the control group using tools to monitor the mosquito density (1 OVT; 1 Double BR-ovt; monthly capture of alates) and the experimental group with control actions using surveillance tools in an intensified way (2 OVTs; 2 Double BR-ovts; fortnightly capture of alates; toxic baits). We evaluated the study's impact on the mosquito density via the Egg Density (ED) and Adult Density (AD) over a period of 12 cycles of 28 days each. The collected adult mosquitoes were processed via RT-qPCR for DENV, CHIKV and ZIKV and, subsequently, the Minimum Infection Rate (MIR) was calculated. After 12 cycles, we observed a 91% and 99% reduction in Aedes ED and AD in the monitored properties, as well as a 76% reduction in the AD of Cx. quinquefasciatus in the same properties. Moreover, we detected circulating arboviruses (DENV and ZIKV) in 19.52% of captured adult mosquitoes. We show that enhancing entomological surveillance tools can aid in the early detection of possible risk areas based on vector mosquito population numbers. Additionally, the detection of important arboviruses such as ZIKV and DENV raises awareness and allows for a better selection of risk areas and silent virus spread. It offers supplementary information for guiding emergency mosquito control measures in the target area. The goal is to minimize human-vector interactions and, subsequently, to lower the risk of transmitting circulating arboviruses.

PANDAS/PANS in the COVID-19 Age: Autoimmunity and Epstein-Barr Virus Reactivation as Trigger Agents?

COVID-19 impacted the entire world's population, frequently resulting in long-lasting neuropsychiatric complications. Furthermore, social distancing, lockdowns and fear for one's personal health worsen individual psychological wellbeing, especially in children and adolescents. Herein, we discuss the results of studies that specifically reported data about the impact of the COVID-19 pandemic or infection on children with Pediatric Acute-Onset Neuropsychiatric Disorders (PANS). Furthermore, we present the cases of five adolescents with PANS whose symptomatology increased following SARS-CoV-2 infection. What emerged from this study was that COVID-19 resulted in the exacerbation of obsessions, tics, anxiety and mood symptoms and decreased wellbeing. Moreover, new symptoms, as well as new PANS cases, are reported to have arisen after COVID-19 infection. Here, we hypothesize that the pathogenic mechanisms of silent viruses, such as the Epstein-Barr virus, are related to neuroinflammation, immune responses and reactivation, with additional roles played by social-isolation-related inflammatory processes. The discussion of PANS, which represents a model of immune-mediated neuropsychiatric manifestations, is particularly relevant, with the aim of uncovering the mechanisms that lead to neuropsychiatric Post-Acute COVID-19 Syndrome (PACS). Prospects for future studies and treatment implications are discussed.

Photoexcited graphene oxides activate silent viruses in bacteria with dependency on their sizes

Smaller graphene oxides can cut into bacteria and induce lysogenic activation via photo-generated singlet oxygen.

Cutaneous manifestations in children with SARS-CoV-2 infection and/or COVID-19: what do we know after 10 months under this pandemic?

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global crisis. However, cutaneous manifestations in children with SARS‐CoV‐2 infection have received little attention.ObjectiveOur study was aimed to present clinical and cutaneous manifestations of children with SARS‐CoV‐2 and to provide the basis for early diagnosis.MethodsWe analyzed the clinical data of COVID‐19 infected (CI) children worldwide from December 2019 to October 6, 2020, by using search terms “COVID‐19,” “SARS‐CoV‐2,” “Coronavirus” in combination with “cutaneous,” “lesion,” “rash,” “skin,” “dermatology,” “epidermis,” “dermis,” “multisystem inflammatory syndrome.” We collected and analyzed the general information, clinical symptoms, cutaneous manifestations, laboratory examination results, history of close contact with CI patients or suspected CI patients, and outcome in CI children.ResultsAmong 90 CI children, there were 46 boys (59%) and 32 girls (41%). Erythema was the most frequent lesion, followed by conjunctivitis, and edematous lesions. Face was the most commonly affected location including lips, conjunctivae, tongue, eyes, and eyelids. Sixty‐three (73.3%) patients had multisystem inflammatory syndrome (MIS‐C). As for clinical symptoms, 70 (81.4%) CI children suffered fever, and 34 (39.5%) patients had lung involvement. Meanwhile, 65.1% of patients had cardiac involvement, 4.7% of patients were asymptomatic, and 71.6% of patients received intravenous immunoglobulin, as well as 31.1% of CI children received systemic corticosteroids. Three children were dead. The most frequent route of infection was familial clustering. As silent virus carriers of CI children, it is important to find out the clinical and cutaneous manifestations in CI children to prevent and control COVID‐19 transmission.

COVID-19: Experience from KEM Hospital, Mumbai

King Edward Memorial (KEM) Hospital started treating COVID-19 patients in the first week of March 2020. It initially started with a single “isolation ward” and steadily increased to the first and then to the second floors of the heritage building of KEM. A lot of brainstorming, planning, designing the COVID-19 wards, procuring hardware, setting up of back-office teams, creating a “war room,” and putting together “attack teams” were integral components of a herculean task. KEM responded adroitly and started training all health care workers (HCWs) across ranks, that is, medical students, interns, and residents. We never knew how the silent virus was going to attack us. An alien pandemic needed swift action and an emergency policy.

SARS-CoV-2: an unknown agent and challenges in vaccine development

SARS-CoV-2: an unknown agent and challenges in vaccine development

Masculinity beyond repair

This article explores representations of male aging in Jonathan Franzen’s The Corrections (2001) by looking at theories of aging, pathology, and hegemonic masculinity. While, in general, academic discourses about aging tend to link old age to pathology, the focus on gender stereotypes adds another layer to the perception of aging in Franzen’s novel. The Corrections is constructed around an aged patriarch who is not only struck by the illnesses of old age but, more importantly, he keeps clinging to an idealized masculine identity he is no longer able to maintain as an old man. Drawing on the difficulties of identity construction concerning Aging Studies and the lack of what Gabriela Spector-Mersel defines as “masculinity scripts,” my article illustrates how literary representations can construct male losses as symptoms of a silent virus that appears to break out in the aged body. The article will show that these (lived) hegemonic concepts of masculinity establish the male as a dominant collective but simultaneously constitute the inevitable failure of the individual. Hegemonic masculinities then have a disabling impact on the old man as is mirrored in Franzen’s doomed protagonist who becomes the victim of his own concepts of masculinity.

Genetically Intact but Functionally Impaired HIV-1 Env Glycoproteins in the T-Cell Reservoir.

HIV-infected subjects under antiretroviral treatment (ART) harbor a persistent viral reservoir in resting CD4+ T cells, which accounts for the resurgence of HIV replication after ART interruption. A large majority of HIV reservoir genomes are genetically defective, but even among intact proviruses few seem able to generate infectious virus. To understand this phenomenon, we examined the function and expression of HIV envelope glycoproteins reactivated from the reservoir of four HIV-infected subjects under suppressive ART. We studied full-length genetically intact env sequences from both replicative viruses and cell-associated mRNAs. We found that these Env proteins varied extensively in fusogenicity and infectivity, with strongest functional defects found in Envs from cell-associated mRNAs. Env functional impairments were essentially explained by defects in Env protein expression. Our results support the idea that defects in HIV Env expression, preventing cytopathic or immune HIV clearance, contribute to the persistence of the HIV T-cell reservoir in vivoIMPORTANCE In most individuals, evolution of HIV infection is efficiently controlled on the long-term by combination antiviral therapies. These treatments, however, fail to eradicate HIV from the infected subjects, a failure that results both in resurgence of virus replication and in resumption of HIV pathogenicity when the treatment is stopped. HIV resurgence, in these instances, is widely assumed to emerge from a reservoir of silent virus integrated in the genomes of a small number of T lymphocytes. The silent HIV reservoir is mostly composed of heavily deleted or mutated HIV DNA. Moreover, among the seemingly intact remaining HIV, only very few are actually able to efficiently propagate in tissue culture. In this study, we find that intact HIV in the reservoir often carry strong defects in their capacity to promote fusion to neighboring cells and infection of target cells, a defect related to the function and expression of the HIV envelope glycoprotein. Impaired envelope glycoprotein expression and function could explain why cells harboring these viruses tend to remain undetected and unharmed in the reservoir.

Infectious Agents are Associated with Psychiatric Diseases.

There are several infectious agents in the environment that can cause persistent infections in the host. They usually cause their symptoms shortly after first infection and later persist as silent viruses and bacteria within the body. However, these chronic infections may play an important role in the pathogenesis of schizophrenia and Tourette’s syndrome (TS). We investigated the distribution of different neurotrophic infectious agents in TS, schizophrenia and controls. A total of 93 individuals were included (schizophrenic patients, Tourette patients and controls). We evaluated antibodies against cytomegalovirus (CMV), herpes-simplex virus (HSV), Epstein-Barr virus, Toxoplasma, Mycoplasma and Chlamydia trachomatis/pneumoniae. By comparing schizophrenia and TS, we found a higher prevalence of HSV (P=0.017) and CMV (P=0.017) antibodies in schizophrenic patients. Considering the relationship between schizophrenia, TS and healthy controls, we showed that there are associations for Chlamydia trachomatis (P=0.007), HSV (P=0.027) and CMV (P=0.029). When all measured viruses, bacteria and protozoa were combined, schizophrenic patients had a higher rate of antibodies to infectious agents than TS patients (P=0.049). Tourette and schizophrenic patients show a different vulnerability to infectious agents. Schizophrenic patients were found to have a higher susceptibility to viral infections than individuals with TS. This finding might point to a modification in special immune parameters in these diseases.

Multiple dose vaccination with heterologous H5N2 vaccine: Immune response and protection against variant clade 2.2.1 highly pathogenic avian influenza H5N1 in broiler breeder chickens

Circulation of an antigenically variant lineage of highly pathogenic avian influenza (HPAI) H5N1 virus in chicken breeder flocks in Egypt is a continuing problem. The protective efficacy of multiple repeated vaccinations using the currently available H5N2 vaccines is unclear. Here, broiler breeder chickens were vaccinated at weeks 6, 12 and 18 with an inactivated H5N2 commercial vaccine. HI-titer against an Egyptian H5N1 field isolate of classic clade 2.2.1 (EGYcls/H5N1) were significantly lower after the first immunization but increased after booster vaccinations. In contrast, no HI titers were induced against an antigenically distinct field virus of the variant lineage of clade 2.2.1 (EGYvar/H5N1). Upon challenge at week 50 mild, if any, clinical signs were observed in the group infected with EGYcls/H5N1 although one of eight (12.5%) birds died. Mortality reached 6/8 (75%) in the EGYvar/H5N1 challenge group. Virus excretion in all vaccinated groups was reduced in amplitude, but in vaccinated surviving birds, time of virus excretion was extended to up to ten days. Strikingly, challenged vaccinated birds kept laying eggs almost throughout the observation period. Virus was detected on the outer egg-shell of 17 of 40 eggs. The majority of the infected eggs were derived from the EGYcls/H5N1 challenged animals; here the virus was detected also in the yolk and albumin. Repeated vaccination using a commercial H5N2-based vaccine broadened the antigen profile of induced antibodies but did not provide adequate protection against heterologous virus variant. In addition, the observation of AIV contaminated eggs from infected flocks highlights the risk of silent virus spread by vaccinated animals and point to eggs as a possible vector.

Les complications infectieuses liées à l’utilisation des anticorps monoclonaux chez l’homme

The large experience accumulated with the therapeutic use of monoclonal antibodies has revealed undesirable effects, among which opportunistic infections when prescribed in inflammatory or hematological diseases. This deleterious effect is a direct consequence of the immunosuppression induced by these antibodies through the blockade of several key pathways involved in both innate and adaptative immune responses, including migration of effector cells, depletion of B or T lymphocytes, inhibition of key cell-cell interactions. Four antibodies are concerned, targeting CD52, CD20, TNF-a and VLA-4, and major risks include activation of latent tuberculosis, or of normally silent viruses. Precise evaluation of these risks and understanding of their mechanisms have now led to the improvement of clinical safety, based on the detection of patients at risk, weighting of the benefit/risk ratio, and a very rigorous detection of latent infections before the onset of treatment by monoclonal antibodies know to induce immunosuppression.

Dendritic cells harbor infectious porcine circovirus type 2 in the absence of apparent cell modulation or replication of the virus.

Dendritic cells (DCs) play crucial roles in innate and adaptive immune responses, rendering them critical targets for virus infections. Porcine circovirus type 2 (PCV2) is associated with the development of postweaning multisystemic wasting syndrome (PMWS) in piglets. We demonstrate here that 80 to 90% of monocyte-derived and bone marrow-derived DCs interact with PCV2 similar to the early stages of an infection. There was no evidence for virus replication, but the virus did persist in DCs without loss of infectivity nor the induction of cell death. This could reflect an abortive infection, but there was no evidence of virus uncoating-the infectivity remained intact for at least 5 days. Alternatively, the results may reflect DC endocytosis of antigenic material. However, there was no modulation of DC surface major histocompatibility complex class I and class II, CD80/86, CD25, CD16, or CD14. Furthermore, infected DC did not transmit virus to syngeneic T lymphocytes, even when the latter were activated. Such coculture did not induce PCV2 replication or death of the lymphocytes or DCs. These results demonstrate that PCV2 can persist in DCs in the absence of virus replication or degradation. Such a silent virus infection presents a novel mechanism of not only immune evasion but also escaping the DC degradation pathway. Because of their migratory capacity, infection of DCs thus provides a potent vehicle for transport of the virus throughout the host without the need for replication. In addition, the lymphopenia seen in PMWS is not a direct effect of the virus on lymphocytes but would require additional events, as proposed by others.

Failure to demonstrate a role for line I b tumor-associated surface antigen in the etiology of age-dependent polioencephalomyelitis

In the preceeding paper [Morris et al. (1982), Molne. Immun. 19, 973–982] we demonstrate an associative interaction between the line I b tumor-associated surface antigen (I b-TASA) and the D k/K k regions of the major histocompatibility complex, i.e. ‘altered-self’ antigen. We originally hypothesized that age-dependent polioencephalomyelitis (ADPE) occurred as the result of immune recognition of a ‘self’-determinant on the ‘altered-self’ antigen. In this report we used the non-ionic detergent. NP-40, to solubilize I b cell surface antigens. Although immunization of immunocompetent C58 mice with the soluble NP-40 I b cell extract afforded protection to lethal tumor challenge, the extract failed to induce ADPE in immunosuppressed mice. Data presented here demonstrate that I b-TASA is not involved in the etiology of ADPE. The evidence suggests that lactic dehydrogenase virus, which is a silent virus passaged with line I b leukemia, is the causative agent of the paralytic disease.

Effect of an acute viral infection by a silent virus on the humoral immune responses.

Investigations on the effect of virus infections on the host’s immune system started almost twenty years ago when Peterson et al. demonstrated that Gross virus-infected mice are impaired in their ability to respond in antibody production to the T2 bacteriophage (1). Similar findings were reported in animals infected with other oncogenic viruses, such as Moloney, Friend or Rauscher leukemia viruses (2–4). Viruses which do not cause leukemia but infect lymphoid tissue were also found to modulate immune responses. Thus Aleutian mink disease virus (5), lymphocytic choriomeningitis virus (6) and M-P virus (7) were found to degress the host humoral responses to sheep erythrocytes (SRBC), while Venezuelan equine encephalitis virus (8) and lactic dehydrogenase virus (LDV; 9–14) were found to enhance antibody responses to human gamma globulin (HGG) or SRBC.

Characterization of Human TK- Cell Lines Transformed to a TK+ Phenotype by Herpes Simplex Virus Type 2 DNA

Human TK- cells carrying the HSV-2 TK gene as a result of transformation with virus DNA express a TK activity of virus origin and maintain the TK+ phenotype when grown in HAT medium. Under non-selective conditions, however, reversion to a TK- phenotype occurs with a significant frequency characteristic of each transformed line. Once reversion has occurred the TK- phenotype appears to be stable, since only very rare instances of TK- to TK+ reversion have been observed. TK- revertants were susceptible to re-transformation by virus DNA, but no reactivation of a silent virus TK gene could be obtained by superinfecting them with a TK- virus mutant. The data presented are consistent with the hypothesis that acquisition of the TK- phenotype is brought about by loss of the virus sequences coding for TK.

Lactic dehydrogenase virus.

Inapparent virus infections of experimental animals and tissue culture systems present to the investigator a problem which it is impossible to overcome completely. Although all recognised viruses can be excluded from an experimental system, previously unsuspected viruses causing no obvious effects (‘silent’ viruses) will continue to be discovered. A truly silent virus would replicate, causing no change in its host cell, damage to infected tissue or immune response and would presumably be of no consequence. It is the relatively silent viruses which cause virtually no pathological changes but can alter the response of a test system, which are important. The lactic dehydrogenase virus (LDV) is an interesting example of such a virus. It causes no clinical disease in mice but can significantly alter their response to other infective agents and to the development of tumours. If the ideal virus is one which replicates rapidly and continuously without killing its host and is easily transmitted, LDV must be almost perfect. It replicates very rapidly in mice of all strains so far tested, produces a stable infection with a continuously high level of infective virus in the blood for the remainder of the animal’s life, yet causes no harm to its host. It lacks, however, one important property; the ability to pass readily from one animal to another under natural conditions. Infected females often fail to infect their young and transmission between adults is not very frequent. However, no doubt because of the permanence of the infected state, the virus survives in wild mice and is easily transmitted inadvertently by experimental procedures.KeywordsInfected MouseNewcastle Disease VirusGamma GlobulinUninfected MousePlasma EnzymeThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Riley virus neutralizing activity in the plasma of infected mice with persistent viraemia

Lactate dehydrogenase-elevating virus (LDV) is a mouse arterivirus, unusual in its extreme host specificity and its persistence in the circulation of the infected host that naturally infects wild mice. Although, probably not as frequent in laboratory mouse colonies as it used to be, LDV infection may affect experimental results, primarily through its effects on the host immune responses. On the other hand, because of its unique properties, LDV infections serve as a good animal model for viral persistence, virally induced immunomodulation, and pathogenic infection of neurons in the central nervous system. However, the inability of LDV to infect in transformed cell lines and to cause a detectable cytopathic effect in cell cultures in which it replicates, such as mouse peritoneal exudate cells, represents technical obstacles to the further analysis of this virus. Identification of the cell receptor utilized by LDV would constitute a major advance, since this might lead to the creation of a cell line permissive to LDV infection. Whereas LDV is a natural and sometimes pathogenic infectious agent of the mouse, it does not currently represent a major threat to animal facilities. The virus is not very contagious and there are a number of easy methods available to detect infected mice. Moreover, further study of the interaction between relatively silent viruses, such as LDV, and their host species should lead to new insights into the mechanisms by which viruses can establish and maintain relatively harmless, persistent infections in their hosts.