scholarly journals HCMV Antivirals and Strategies to Target the Latent Reservoir

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 817
Author(s):  
Marianne R. Perera ◽  
Mark R. Wills ◽  
John H. Sinclair
Keyword(s):  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Latent Infection ◽  
Severe Disease ◽  
Unmet Need ◽  
Human Herpesvirus ◽  
Viral Resistance ◽  
Latent Reservoir ◽  
Transplant Recipients ◽  
Hcmv Disease

Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus. In healthy people, primary infection is generally asymptomatic, and the virus can go on to establish lifelong latency in cells of the myeloid lineage. However, HCMV often causes severe disease in the immunosuppressed: transplant recipients and people living with AIDS, and also in the immunonaive foetus. At present, there are several antiviral drugs licensed to control HCMV disease. However, these are all faced with problems of poor bioavailability, toxicity and rapidly emerging viral resistance. Furthermore, none of them are capable of fully clearing the virus from the host, as they do not target latent infection. Consequently, reactivation from latency is a significant source of disease, and there remains an unmet need for treatments that also target latent infection. This review briefly summarises the most common HCMV antivirals used in clinic at present and discusses current research into targeting the latent HCMV reservoir.

scholarly journals Probable Donor-Derived Human Adenovirus Type 34 Infection in 2 Kidney Transplant Recipients From the Same Donor

2018 ◽  
Vol 6 (3) ◽  
Author(s):  
Matthew A Pettengill ◽  
Tara M Babu ◽  
Paritosh Prasad ◽  
Sally Chuang ◽  
Michael G Drage ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Primary Infection ◽  
Latent Infection ◽  
Tubulointerstitial Nephritis ◽  
Hemorrhagic Cystitis ◽  
Organ Donor ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Abstract Human adenovirus type 34 (HAdV-34) infection is a recognized cause of transplant-associated hemorrhagic cystitis and, in rare cases, tubulointerstitial nephritis. The source of such infections is often difficult to assess, that is, whether acquired as a primary infection, exposure to a pathogen in the transplanted organ, or reactivation of an endogenous latent infection. We present here 2 cases of likely transplant-acquired HAdV-34 infection from the same organ donor, manifesting as tubulointerstitial nephritis in 1.

scholarly journals Human Cytomegalovirus-Encoded microRNAs Can Be Found in Saliva Samples from Renal Transplant Recipients

2020 ◽  
Vol 6 (4) ◽  
pp. 50
Author(s):  
Shelley Waters ◽  
Silvia Lee ◽  
Kylie Munyard ◽  
Ashley Irish ◽  
Patricia Price ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Immune Responses ◽  
Human Cytomegalovirus ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Host Immune Responses ◽  
Cell Responses ◽  
Hcmv Disease ◽  
Mirna Species

Human cytomegalovirus (HCMV) infections are common following renal transplantation and may have long-lasting effects. HCMV can be measured directly by viral DNA or indirectly via host immune responses. HCMV-encoded microRNA (miRNA) may alter the pathobiology of HCMV infections and contribute to the progression of HCMV disease. HCMV-encoded miRNAs can be detected in blood but have not been sought in saliva. We investigated saliva samples from 32 renal transplant recipients (RTR) and 12 seropositive healthy controls for whom immunological data was available. Five HCMV-encoded miRNAs (miR-UL112-5p, miR-US5-2-3p, miR-UL36, miR-US25-2-3p and miR-UL22A) were sought using primer probe assays. HCMV miRNA species were detected in saliva from 15 RTR and 3 healthy controls, with miR-US5-2-3p most commonly detected. The presence of HCMV miRNAs associated with increased T-cell responses to HCMV IE-1 in RTR, suggesting a link with frequent reactivations of HCMV.

scholarly journals Diagnosis and Management of Human Cytomegalovirus Infection in the Mother, Fetus, and Newborn Infant

2002 ◽  
Vol 15 (4) ◽  
pp. 680-715 ◽  
Author(s):  
Maria Grazia Revello ◽  
Giuseppe Gerna
Keyword(s):  
Prenatal Diagnosis ◽  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Hcmv Infection ◽  
Prognostic Markers ◽  
Recurrent Infection ◽  
Congenital Infection ◽  
Immunoglobulin M ◽  
Hcmv Disease ◽  
The Impact

SUMMARY Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection and mental retardation. HCMV infection, while causing asymptomatic infections in most immunocompetent subjects, can be transmitted during pregnancy from the mother with primary (and also recurrent) infection to the fetus. Hence, careful diagnosis of primary infection is required in the pregnant woman based on the most sensitive serologic assays (immunoglobulin M [IgM] and IgG avidity assays) and conventional virologic and molecular procedures for virus detection in blood. Maternal prognostic markers of fetal infection are still under investigation. If primary infection is diagnosed in a timely manner, prenatal diagnosis can be offered, including the search for virus and virus components in fetal blood and amniotic fluid, with fetal prognostic markers of HCMV disease still to be defined. However, the final step for definite diagnosis of congenital HCMV infection is detection of virus in the blood or urine in the first 1 to 2 weeks of life. To date, treatment of congenital infection with antiviral drugs is only palliative both prior to and after birth, whereas the only efficacious preventive measure seems to be the development of a safe and immunogenic vaccine, including recombinant, subunit, DNA, and peptide-based vaccines now under investigation. The following controversial issues are discussed in the light of the most recent advances in the field: the actual perception of the problem; universal serologic screening before pregnancy; the impact of correct counseling on decision making by the couple involved; the role of prenatal diagnosis in ascertaining transmission of virus to the fetus; the impact of preconceptional and periconceptional infections on the prevalence of congenital infection; and the prevalence of congenitally infected babies born to mothers who were immune prior to pregnancy compared to the number born to mothers undergoing primary infection during pregnancy.

Development of a LUX real-time PCR for the detection and quantification of human herpesvirus 7

2009 ◽  
Vol 55 (3) ◽  
pp. 319-325 ◽  
Author(s):  
Massimiliano Bergallo ◽  
Cristina Costa ◽  
Maria Elena Terlizzi ◽  
Francesca Sidoti ◽  
Samuela Margio ◽  
...  
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Primary Infection ◽  
Latent Infection ◽  
Dynamic Range ◽  
Human Herpesvirus ◽  
Clinical Samples ◽  
House Light ◽  
Pcr Assay ◽  
Sensitivity Specificity

Human herpesvirus 7 is a highly seroprevalent β-herpesvirus that, following primary infection, remains latent in CD4+ T cells and determines a persistent rather than a latent infection in various tissues and organs, including the lung and skin. This paper describes the development of an in-house light upon extension real-time PCR assay for quantification of human herpesvirus 7 DNA in clinical samples. The efficiency, sensitivity, specificity, inter- and intra-assay variability, and dynamic range have been determined. Subsequently, the assay has been validated by evaluating the human herpesvirus 7 load in bronchoalveolar lavages and skin specimens, chosen as 2 persistency sites, from healthy and pathological individuals. The real-time PCR assay developed in this study could be a useful tool to detect and quantify human herpesvirus 7 DNA in different clinical specimens to elucidate its epidemiological and pathogenic roles.

Human Herpesvirus 7 Primary Infection in Kidney Transplant Recipients

2008 ◽  
Vol 85 (2) ◽  
pp. 298-302 ◽  
Author(s):  
Andrés Antón ◽  
Carlos Cervera ◽  
Tomás Pumarola ◽  
Asunción Moreno ◽  
Natividad Benito ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Primary Infection ◽  
Human Herpesvirus ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

Severe fetal symptomatic infection from human cytomegalovirus following non-primary maternal infection: report of two cases

2021 ◽  
Author(s):  
Mariano Matteo Lanna ◽  
Elisa Fabbri ◽  
Maurizio Zavattoni ◽  
Chiara Doneda ◽  
Valentina Toto ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Primary Infection ◽  
Fetal Brain ◽  
Cortical Plate ◽  
Maternal Infection ◽  
Cerebral Lesions ◽  
Morphological Pattern ◽  
First Case ◽  
Hcmv Disease ◽  
The Impact

Introduction Human cytomegalovirus (HCMV) is the most common congenital infection, expecially severe after a maternal primary infection; sequelae in neonates born to mothers experiencing a non-primary infection have been already reported. Hereby, two cases of severe fetal HCMV disease in seroimmune gravidas referred to our Unit are described. Cases presentation Case 1 A fetus at 21 weeks’ gestation with signs of anemia and brain abnormalities at ultrasound (US), described at magnetic resonance (MR) imaging as ependymal irregularity and bilateral asymmetric parenchimal thinning; amniotic fluid sample was positive for HCMV although the woman had a previous immunity; after termination of pregnancy, autopsy demonstrated a thicken layer of disorganized neurons on the right cortical plate, while on the left there was a morphological pattern coherent with polymicrogyria. Case 2 A fetus at 20 weeks’ gestation with anemia, moderate atrio-ventricular insufficiency, hepatosplenomegaly but no major cerebral lesions. Fetal blood was positive for HCMV, although unexpected for pre-pregnancy maternal immunity, and intrauterine transfusion was needed. A cesarean section at 34 weeks gestation was performed due to worsening condition of the fetus, who had a birthweight of 2210 grams, needed platelet transfusions but MR examination and clinical evaluation were normal. Conclusion The impact of non-primary maternal infection on pregnancy outcome is unknown and fetal brain damage in HCMV seroimmune transmitter-mothers can occur as a consequence of maternal re-infection or reactivation for a hypotetic different role of HCMV-primed CD4+ or CD8+ T-cells in fetal brain, with progressive brain lesions coexistent in the first case and with severe unexpected anemia in the second case. A previous maternal HCMV immunity should not exempt to test anemic fetuses for such infection, nor to consider a potential transplacental transmission.

Epstein–Barr virus

2010 ◽  
pp. 501-508 ◽  
Author(s):  
M.A. Epstein ◽  
A.B. Rickinson
Keyword(s):  
B Cells ◽  
Epithelial Cells ◽  
Primary Infection ◽  
Epstein Barr Virus ◽  
Latent Infection ◽  
Human Herpesvirus ◽  
Carrier State ◽  
Barr Virus ◽  
Double Stranded Dna ◽  
Epstein Barr

Epstein–Barr virus (EBV) is a human herpesvirus with a linear double-stranded DNA genome that is carried asymptomatically by most people. Symptomless primary infection is usual in childhood, establishing a lifelong carrier state where the virus persists as a latent infection of circulating B cells. The virus replicates recurrently in oropharyngeal epithelial cells, with consequent shedding of virus in saliva transmitting infection....

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