Human cytomegalovirus
[4] HCMV infection is typically unnoticed in healthy people, but can be life-threatening for the immunocompromised, such as HIV-infected persons, organ transplant recipients, or newborn infants.
"[18] Human cytomegalovirus infection has a classic triad of symptoms: fever, peaking in the late afternoon or early evening; pharyngitis, usually exudative; and symmetrical adenopathy.
[4] Infection requires close, intimate contact with a person secreting the virus in their saliva, urine, or other bodily fluids.
[28] In disseminated cytomegalovirus infections, as may be seen in the context of an immunosuppressed host, the virus is readily transmitted between polymorphonuclear leukocytes (PM-NLs) and endothelial cells.
Another five percent later develop cerebral calcification (decreasing IQ levels dramatically and causing sensorineural deafness and psychomotor retardation).
[citation needed] However, infants born preterm and infected with HCMV after birth may experience cognitive and motor impairments later in life.
[38] Specific disease entities recognized in those people are People without CMV infection who are given organ transplants from CMV-infected donors require prophylactic treatment with valganciclovir (ideally) or ganciclovir, and regular serological monitoring to detect a rising CMV titre; if treated early establishment of a potentially life-threatening infection can be prevented.
[citation needed] Infectious CMV may be shed in the bodily fluids of any infected person, and can be found in urine, saliva, blood, tears, semen, and breast milk.
[49] Researchers also found that when the cells were infected with CMV, they created renin, a protein known to contribute to high blood pressure.
These ligands are normally upregulated in times of cellular stress, such as in viral infection, and by preventing their upregulation, CMV can prevent its host cell from dying due to NK cells[54] A substantial portion of the immune system is involved in continuously controlling CMV, which drains the resources of the immune system.
[55][56] Death rates from infectious disease accelerate with age,[57] and CMV infection correlates with reduced effectiveness of vaccination.
In addition, the virus can be cultured from specimens obtained from urine, throat swabs, bronchial lavages and tissue samples to detect active infection.
The CMV pp65 antigenemia test is an immunofluorescence-based assay which utilizes an indirect immunofluorescence technique for identifying the pp65 protein of cytomegalovirus in peripheral blood leukocytes.
The advantage of this assay is the rapidity in providing results in a few hours and that the pp65 antigen determination represents a useful criterion for the physician to initiate antiviral therapy.
[62][63] An ELISA technique for CMV-specific IgM is available, but may give false-positive results unless steps are taken to remove rheumatoid factor or most of the IgG antibody before the serum sample is tested.
Only virus recovered from a target organ, such as the lung, provides unequivocal evidence that the current illness is caused by acquired CMV infection.
If serologic tests detect a positive or high titer of IgG, this result should not automatically be interpreted to mean that active CMV infection is present.
[64] During allogeneic hematopoietic stem cell transplant, it is generally advised to match the serostatus of donor and recipient.
Conversely, a seropositive recipient is at risk of viral reactivation if they receive a transplant from a seronegative donor, losing their innate defenses in the process.
In general, the risk is highest for CMV seropositive recipients, in which viral reactivation is a cause of significant morbidity.
[65][66] A phase 2 study of a CMV-vaccine published in 2009 indicated an efficacy of 50%—the protection provided was limited, and a number of subjects contracted CMV infection despite vaccination.
[67] In 2013, Astellas Pharma started on individuals who received a hematopoietic stem cell transplant a phase 3 trial with its CMV deoxyribonucleic acid DNA cytomegalovirus vaccine ASP0113.
[70][71] The Centers for Disease Control and Prevention (CDC) recommend regular hand washing,[72] especially after changing diapers.
Alone or in combination with an antiviral agent, it has been shown to: Ganciclovir (Cytovene) treatment is used for people with depressed immunity who have either sight-related or life-threatening illnesses.
A variety of amino acid changes in the UL97 protein kinase and the viral DNA polymerase have been reported to cause drug resistance.
A better understanding of how HCMV supports viral latency and reactivation should allow for the development of new therapies that target the latent reservoir.
It directly inhibits polymerase function by blocking the pyrophosphate binding site of pUL54 (note: investigational drug letermovir acts through a mechanism that involves viral terminase).
Genotypic resistance testing is becoming the method of choice because it is faster, but requires previous phenotypic characterisation of each newly found mutation.
This can be performed via a web-based search tool Archived 9 January 2016 at the Wayback Machine that links a person's HCMV sequence to a database containing all published UL97 and UL54 mutations and corresponding antiviral drug susceptibility phenotypes.
