Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

Human Cytomegalovirus (HCMV) is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n=50) and from benign meningioma patients (n=30) were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG) compared to 72.5% among control samples (P=0.04). These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis.

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The Zinc Finger Antiviral Protein ZAP Restricts Human Cytomegalovirus and Selectively Binds and Destabilizes Viral UL4/UL5 Transcripts

mBio ◽

10.1128/mbio.02683-20 ◽

2021 ◽

Vol 12 (3) ◽

Author(s):

Ana Cristina Gonzalez-Perez ◽

Markus Stempel ◽

Emanuel Wyler ◽

Christian Urban ◽

Antonio Piras ◽

...

Keyword(s):

Gene Expression ◽

Zinc Finger ◽

Human Cytomegalovirus ◽

Hcmv Infection ◽

Viral Infections ◽

Economic Losses ◽

Sequencing Analysis ◽

Antiviral Protein ◽

Hcmv Replication

ABSTRACT Interferon-stimulated gene products (ISGs) play a crucial role in early infection control. The ISG zinc finger CCCH-type antiviral protein 1 (ZAP/ZC3HAV1) antagonizes several RNA viruses by binding to CG-rich RNA sequences, whereas its effect on DNA viruses is less well understood. Here, we decipher the role of ZAP in the context of human cytomegalovirus (HCMV) infection, a β-herpesvirus that is associated with high morbidity in immunosuppressed individuals and newborns. We show that expression of the two major isoforms of ZAP, ZAP-S and ZAP-L, is induced during HCMV infection and that both negatively affect HCMV replication. Transcriptome and proteome analyses demonstrated that the expression of ZAP results in reduced viral mRNA and protein levels and decelerates the progression of HCMV infection. Metabolic RNA labeling combined with high-throughput sequencing (SLAM-seq) revealed that most of the gene expression changes late in infection result from the general attenuation of HCMV. Furthermore, at early stages of infection, ZAP restricts HCMV by destabilizing a distinct subset of viral mRNAs, particularly those from the previously uncharacterized UL4-UL6 HCMV gene locus. Through enhanced cross-linking immunoprecipitation and sequencing analysis (eCLIP-seq), we identified the transcripts expressed from this HCMV locus as the direct targets of ZAP. Moreover, our data show that ZAP preferentially recognizes not only CG, but also other cytosine-rich sequences, thereby expanding its target specificity. In summary, this report is the first to reveal direct targets of ZAP during HCMV infection, which strongly indicates that transcripts from the UL4-UL6 locus may play an important role for HCMV replication. IMPORTANCE Viral infections have a large impact on society, leading to major human and economic losses and even global instability. So far, many viral infections, including human cytomegalovirus (HCMV) infection, are treated with a small repertoire of drugs, often accompanied by the occurrence of resistant mutants. There is no licensed HCMV vaccine in sight to protect those most at risk, particularly immunocompromised individuals or pregnant women who might otherwise transmit the virus to the fetus. Thus, the identification of novel intervention strategies is urgently required. In this study, we show that ZAP decelerates the viral gene expression cascade, presumably by selectively handpicking a distinct set of viral transcripts for degradation. Our study illustrates the potent role of ZAP as an HCMV restriction factor and sheds light on a possible role for UL4 and/or UL5 early during infection, paving a new avenue for the exploration of potential targets for novel therapies.

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Nonenvelopment Role for the ESCRT-III Complex during Human Cytomegalovirus Infection

Journal of Virology ◽

10.1128/jvi.02096-17 ◽

2018 ◽

Vol 92 (12) ◽

Cited By ~ 10

Author(s):

Nicholas T. Streck ◽

Jillian Carmichael ◽

Nicholas J. Buchkovich

Keyword(s):

Human Cytomegalovirus ◽

Hcmv Infection ◽

Viral Infections ◽

Virus Production ◽

Opportunistic Pathogen ◽

Inducible Expression ◽

Dominant Negative ◽

Aaa Atpase ◽

Viral Budding

ABSTRACTSecondary envelopment of human cytomegalovirus (HCMV) occurs through a mechanism that is poorly understood. Many enveloped viruses utilize the endosomal sorting complexes required for transport (ESCRTs) for viral budding and envelopment. Although there are conflicting reports on the role of the ESCRT AAA ATPase protein VPS4 in HCMV infection, VPS4 may act in an envelopment role similar to its function during other viral infections. Because VPS4 is normally recruited by the ESCRT-III complex, we hypothesized that ESCRT-III subunits would also be required for HCMV infection. We investigated the role of ESCRT-III, the core ESCRT scission complex, during the late stages of infection. We show that inducible expression of dominant negative ESCRT-III subunits during infection blocks endogenous ESCRT function but does not inhibit virus production. We also show that HCMV forms enveloped intracellular and extracellular virions in the presence of dominant negative ESCRT-III subunits, suggesting that ESCRT-III is not involved in the envelopment of HCMV. We also found that as with ESCRT-III, inducible expression of a dominant negative form of VPS4A did not inhibit the envelopment of virions or reduce virus titers. Thus, HCMV does not require the ESCRTs for secondary envelopment. However, we found that ESCRT-III subunits are required for efficient virus spread. This suggests a role for ESCRT-III during the spread of HCMV that is independent of viral envelopment.IMPORTANCEHuman cytomegalovirus (HCMV) is a prevalent opportunistic pathogen in the human population. For neonatal and immunocompromised patients, HCMV infection can cause severe and possibly life-threatening complications. It is important to define the mechanisms of the viral replication cycle in order to identify potential targets for new therapies. Secondary envelopment, or acquisition of the membrane envelope, of HCMV is a mechanism that needs further study. Using an inducible fibroblast system to carefully control for the toxicity associated with blocking ESCRT-III function, this study determines that the ESCRT proteins are not required for viral envelopment. However, the study does discover a nonenvelopment role for the ESCRT-III complex in the efficient spread of the virus. Thus, this study advances our understanding of an important process essential for the replication of HCMV.

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Role of Rasayana in Prevention of COVID-19 - A Review

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl1.3072 ◽

2020 ◽

Vol 11 (SPL1) ◽

pp. 716-722

Author(s):

Sneha Dhakite ◽

Sadhana Misar Wajpeyi

Keyword(s):

Immune System ◽

Respiratory System ◽

Viral Infections ◽

Cost Effective ◽

The Body ◽

Healthy Life ◽

Vital Functions ◽

Healthy Life Style ◽

And Control

The “Coronavirus disease 19 (COVID-19)” is caused by “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)”, a newly discovered member of the Coronaviridae family of viruses which is a highly communicable. There is no effective medical treatment till date for Coronavirus disease hence prevention is the best way to keep disease away. Rasayana proved to be highly efficacious and cost effective for the Prevention and Control of viral infections when vaccines and standard therapies are lacking. Rasayana Chikitsa is one of the eight branches of Ashtanga Ayurveda which helps to maintain healthy life style. Rasayana improves immunity and performs many vital functions of human body. Vyadhikshamatva that is immune mechanism of the body is involved in Prevention of the occurrence of a new disease and it also decreases the virulence and progression of an existing disease. In COVID-19 the Respiratory system mainly get affected which is evident from its symptoms like cold, cough and breathlessness. Here the drugs help in enhancing immune system and strengthening functions of Respiratory system can be useful. For this purpose, the Rasayana like Chyavanprasha, Agastya Haritaki, Pippali Rasayana, Guduchi, Yashtimadhu, Haridra, Ashwagandha, Tulsi are used. Rasayana working on Respiratory system are best for Prevention of Coronavirus and boosting immune system. Rasayana Chikitsa can be effective in the Prevention as well as reducing symptoms of COVID-19.

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Role of Mitochondria in Viral Infections

Life ◽

10.3390/life11030232 ◽

2021 ◽

Vol 11 (3) ◽

pp. 232

Author(s):

Srikanth Elesela ◽

Nicholas W. Lukacs

Keyword(s):

Viral Infections ◽

Mitochondrial Dynamics ◽

The Body ◽

Viral Diseases ◽

Multiple Organs ◽

Innate Immune Signaling ◽

Mitochondrial Functions ◽

Host Virus Interactions ◽

Virus Interactions

Viral diseases account for an increasing proportion of deaths worldwide. Viruses maneuver host cell machinery in an attempt to subvert the intracellular environment favorable for their replication. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections. Viruses affect mitochondrial functions and impact mitochondrial metabolism, and innate immune signaling. Resurgence of host-virus interactions in recent literature emphasizes the key role of mitochondria and host metabolism on viral life processes. Mitochondrial dysfunction leads to damage of mitochondria that generate toxic compounds, importantly mitochondrial DNA, inducing systemic toxicity, leading to damage of multiple organs in the body. Mitochondrial dynamics and mitophagy are essential for the maintenance of mitochondrial quality control and homeostasis. Therefore, metabolic antagonists may be essential to gain a better understanding of viral diseases and develop effective antiviral therapeutics. This review briefly discusses how viruses exploit mitochondrial dynamics for virus proliferation and induce associated diseases.

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Role of cannabinoids in various diseases: A review

Current Pharmaceutical Biotechnology ◽

10.2174/1389201023666211223164656 ◽

2021 ◽

Vol 23 ◽

Author(s):

Simran Kaur ◽

Nikita Sharma ◽

Arpita Roy

Keyword(s):

Infectious Diseases ◽

Metabolic Disorders ◽

Viral Infections ◽

Cannabis Sativa ◽

Endocannabinoid System ◽

Psychological Disorders ◽

Bioactive Compound ◽

The Body ◽

Therapeutic Aspect

Background: The plant, Cannabis sativa is heavily explored and researched with many industrial and pharmaceutical applications. The medicinal and therapeutic role of cannabis Sativa has been summarized in the paper, citing its mechanism of action and influence on the human body. Diseases like metabolic disorders, infectious diseases, and psychological disorders pose negative and long-term drastic effects on the body like neurodegeneration and other chronic system failures. Several existing literature has proved its effectiveness against such diseases. Objectives: This review aims to provide an overview of the role of cannabinoids in various diseases like metabolic disorders, infectious diseases, and psychological disorders. Method: Various e-resources like Pubmed, Science Direct, and Google Scholar were thoroughly searched and read to form a well-informed and information-heavy manuscript. Here we tried to summaries the therapeutic aspect of Cannabis sativa and its bioactive compound cannabinoids in various diseases. Result: This review highlights the various constituents which are present in Cannabis sativa, the Endocannabinoid system, and the role of cannabinoids in various diseases Conclusion: Recent research on Cannabis has suggested its role in neurodegenerative diseases, inflammation, sleep disorders, pediatric diseases, and their analgesic nature. Therefore, the authors majorly focus on the therapeutic aspect of Cannabis sativa in various diseases. The focus is also on the endocannabinoid system (ECS) and its role in fighting or preventing bacterial, parasitic, fungal, and viral infections.

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The Role of Spices with reference Novel Coronavirus Covid 19

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11ispl1.4038 ◽

2020 ◽

Vol 11 (SPL1) ◽

pp. 1655-1661

Author(s):

Roshna Sukheoji Bhutada ◽

Kritika Umate

Keyword(s):

Viral Infections ◽

The Body ◽

Common People ◽

Supplementary Food ◽

Long Time ◽

Novel Coronavirus ◽

The Right ◽

Common Spices ◽

Physiological Reactions

The need of the day is a brisk lift to the resistant framework to keep it fit, battling today pandemic infections, for example, Covid — 19. One should get the right amount of nutrients from the diet, supplementation regimen to boost the immune system. These spices are always there to make tasty food as well as to protect the body from infectious diseases by building the immunity strong Ayurveda approaches to develop physiological reactions to facilitate immunity. Planning of diet is most important to boost immunity. As per many types of research to provide supplementary food which contains Zinc, Vitamin C, Vitamin D and immunity boosting food such as dealing with plenty of spices for a very long time. These spices include some rare to very common spices which we can found near us. The concern is that these viral infections are very prone to attack weak immunity and take the chance to affect the country to the globe. So the very common spices available will be always helpful to get through this Regular use of a few spices in the very simple form proves its importance as a medicine. In this article a review of spices is done which we are available near us, we are using it in our daily life and we are getting the benefit of these which a common people might not be fully aware of about role of immunity building of the body.

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Strategy of Human Cytomegalovirus To Escape Interferon Beta-Induced APOBEC3G Editing Activity

Journal of Virology ◽

10.1128/jvi.01224-18 ◽

2018 ◽

Vol 92 (19) ◽

Cited By ~ 9

Author(s):

Sara Pautasso ◽

Ganna Galitska ◽

Valentina Dell'Oste ◽

Matteo Biolatti ◽

Rachele Cagliani ◽

...

Keyword(s):

Human Cytomegalovirus ◽

Hot Spots ◽

Interferon Beta ◽

Hcmv Infection ◽

Viral Infections ◽

Innate Immune ◽

Mutational Robustness ◽

Wide Range ◽

Hcmv Replication ◽

Apobec3 Family

ABSTRACTThe apolipoprotein B editing enzyme catalytic subunit 3 (APOBEC3) is a family of DNA cytosine deaminases that mutate and inactivate viral genomes by single-strand DNA editing, thus providing an innate immune response against a wide range of DNA and RNA viruses. In particular, APOBEC3A (A3A), a member of the APOBEC3 family, is induced by human cytomegalovirus (HCMV) in decidual tissues where it efficiently restricts HCMV replication, thereby acting as an intrinsic innate immune effector at the maternal-fetal interface. However, the widespread incidence of congenital HCMV infection implies that HCMV has evolved to counteract APOBEC3-induced mutagenesis through mechanisms that still remain to be fully established. Here, we have assessed gene expression and deaminase activity of various APOBEC3 gene family members in HCMV-infected primary human foreskin fibroblasts (HFFs). Specifically, we show that APOBEC3G (A3G) gene products and, to a lesser degree, those of A3F but not of A3A, are upregulated in HCMV-infected HFFs. We also show that HCMV-mediated induction of A3G expression is mediated by interferon beta (IFN-β), which is produced early during HCMV infection. However, knockout or overexpression of A3G does not affect HCMV replication, indicating that A3G is not a restriction factor for HCMV. Finally, through a bioinformatics approach, we show that HCMV has evolved mutational robustness against IFN-β by limiting the presence of A3G hot spots in essential open reading frames (ORFs) of its genome. Overall, our findings uncover a novel immune evasion strategy by HCMV with profound implications for HCMV infections.IMPORTANCEAPOBEC3 family of proteins plays a pivotal role in intrinsic immunity defense mechanisms against multiple viral infections, including retroviruses, through the deamination activity. However, the currently available data on APOBEC3 editing mechanisms upon HCMV infection remain unclear. In the present study, we show that particularly the APOBEC3G (A3G) member of the deaminase family is strongly induced upon infection with HCMV in fibroblasts and that its upregulation is mediated by IFN-β. Furthermore, we were able to demonstrate that neither A3G knockout nor A3G overexpression appears to modulate HCMV replication, indicating that A3G does not inhibit HCMV replication. This may be explained by HCMV escape strategy from A3G activity through depletion of the preferred nucleotide motifs (hot spots) from its genome. The results may shed light on antiviral potential of APOBEC3 activity during HCMV infection, as well as the viral counteracting mechanisms under A3G-mediated selective pressure.

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Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

Microorganisms ◽

10.3390/microorganisms8071087 ◽

2020 ◽

Vol 8 (7) ◽

pp. 1087

Author(s):

Manuela Donalisio ◽

Simona Cirrincione ◽

Massimo Rittà ◽

Cristina Lamberti ◽

Andrea Civra ◽

...

Keyword(s):

Breast Milk ◽

Extracellular Vesicles ◽

Human Cytomegalovirus ◽

Hcmv Infection ◽

Protective Role ◽

Surface Proteins ◽

Human Colostrum ◽

Clinical Illness

Breast milk is a complex biofluid that nourishes infants, supports their growth and protects them from diseases. However, at the same time, breastfeeding is a transmission route for human cytomegalovirus (HCMV), with preterm infants being at a great risk of congenital disease. The discrepancy between high HCMV transmission rates and the few reported cases of infants with severe clinical illness is likely due to the protective effect of breast milk. The aim of this study was to investigate the anti-HCMV activity of human preterm colostrum and clarify the role of colostrum-derived extracellular vesicles (EVs). Preterm colostrum samples were collected and the EVs were purified and characterized. The in vitro anti-HCMV activity of both colostrum and EVs was tested against HCMV, and the viral replication step inhibited by colostrum-purified EVs was examined. We investigated the putative role EV surface proteins play in impairing HCMV infection using shaving experiments and proteomic analysis. The obtained results confirmed the antiviral action of colostrum against HCMV and demonstrated a remarkable antiviral activity of colostrum-derived EVs. Furthermore, we demonstrated that EVs impair the attachment of HCMV to cells, with EV surface proteins playing a role in mediating this action. These findings contribute to clarifying the mechanisms that underlie the protective role of human colostrum against HCMV infection.

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Knowledge and Expectations on Antibiotic Use among Older Adults in Malaysia: A Cross-Sectional Survey

Geriatrics ◽

10.3390/geriatrics4040061 ◽

2019 ◽

Vol 4 (4) ◽

pp. 61 ◽

Cited By ~ 1

Author(s):

Lai San Kong ◽

Farida Islahudin ◽

Leelavathi Muthupalaniappen ◽

Wei Wen Chong

Keyword(s):

Older Adults ◽

Viral Infections ◽

Antibiotic Use ◽

The Body ◽

Limited Information ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Inappropriate Use ◽

Validated Questionnaire

Antibiotics are commonly prescribed among older adults, and inappropriate use of antibiotics has been noted. However, there is limited information about their knowledge and expectations for antibiotics. This study aimed to assess older adults’ knowledge of antibiotic use and resistance, their expectations for antibiotics and the relationship between knowledge, expectation and inappropriate practices related to antibiotic use. A cross-sectional survey involving respondents aged 60 years and above was conducted, using a validated questionnaire. A lack of knowledge about the role of antibiotics was observed, whereby more than half of the respondents incorrectly believed that antibiotics can treat viral infections (53.5%) and colds and coughs (53.7%). Also, 67.9% of respondents incorrectly believed that antibiotic resistance occurs when the body becomes resistant to antibiotics. Almost half of the respondents would expect antibiotics for symptoms of self-limiting viral infections. Respondents who answered correctly for the role of antibiotics in viral infections were more likely not to expect antibiotics for cold, flu and cough (p < 0.001). Respondents who answered correctly regarding the need to adhere to antibiotics were more likely to have completed their antibiotic course (p < 0.001). Future educational initiatives should provide key information on the role of antibiotics and the importance of complying with antibiotics in this population.

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