HHV-7 is detectable in a variety of transplant settings, both HSCT and solid organ. Direct effects of HHV-7 include fever, rash, myelosuppression, encephalitis, and pneumonitis. Potentially more important are the indirect effects HHV-7 has on CMV disease, invasive fungal disease, and allograft dysfunction. ViraCor’s quantitative HHV-7 DNA PCR assay is used to detect the presence of the virus and track the course of infection.
See below for additional Human Herpes Virus-7 assay and pathogen-specific information. For online ordering methods click here or contact us .
Assay Sheet
Test ID
7000 HHV-7 Real-time qPCR
CPT Code
87799
Clinical Utility
HHV-7 is detectable in a variety of transplant settings, both HSCT and solid organ. Direct effects of HHV-7 include fever, rash, myelosuppression, encephalitis, and pneumonitis. Potentially more important are the indirect effects HHV-7 has on CMV disease, invasive fungal disease, and allograft dysfunction. Quantitative HHV-7 DNA PCR can be used to document the presence of the virus as well as track the course of infection.
Procedure
Extraction of HHV-7 viral DNA from plasma, other biological fluids, or tissues followed by amplification and detection using real-time, quantitative PCR. An internal control is added to ensure the extraction was performed correctly and the PCR reaction was not inhibited.
Specimens
Whole Blood: 3-5 ml submitted in an EDTA tube; ship ambient. CSF: 1 ml fluid frozen; submitted in a sterile, leakproof tube; ship on dry ice. Other: Please inquire.
Specificity
The primers and probes used in this assay are specific for known strains of HHV-7 based on similarity search algorithms. Additionally, no cross reactivity was detected when tested against adenoviruses, BKV, CMV, EBV, HSV-1, HSV-2, HHV-6 variant A, HHV-6 variant B, HHV-8, JCV, parvovirus B19, SV-40, and VZV.
PCR tests are performed pursuant to a license agreement with Roche Molecular Systems, Inc.
This assay was developed and the performance characteristics were determined at ViraCor Laboratories. This test is performed in a CLIA certified laboratory. FDA approval is not required for the performance of this test.
AS07-0108
Pathogen Overview
ABOUT THE HUMAN HERPES VIRUS 7
Human herpesvirus 7 (HHV-7), a member of the Herpesviridae family, was discovered in 1990. It is a member of the Betaherpesvirinae subfamily, along with HHV-6 and cytomegalovirus (CMV). Of the three viruses, HHV-7 is the least pathogenic. Other viruses in the herpesvirus family that infect humans include: HSV-1, HSV-2, CMV, EBV, HHV-6, HHV-7 and HHV-8. All are linear, double-stranded DNA viruses that have a lipid envelope and share the ability to establish lifetime latency in their host following infection. HHV-7 establishes its latency in lymphocytes.
HUMAN HERPES VIRUS 7 CLINICAL MANIFESTATIONS
Similar to HHV-6, an HHV-7 primary infection causes roseola infantum in infants and young children, an undifferentiated, febrile illness that typically lasts about 6 days. Symptoms include a rash on the neck and trunk, mild upper respiratory infection and cervical lymphadenopathy. Complications include febrile seizures, meningitis, encephalitis, and neurological complications in individuals with active CNS infection. Otitis and gastroenteritis have also been reported in these patients.
HHV-7 is typically acquired prior to age 5 and thought to affect over 95% of the population. After primary infection, HHV-7 establishes latency in the host, predisposing individuals to reactivation during periods of time when their immune systems are not functioning properly.
As a result of a high prevalence rate of HHV-7 in the general population, it is thought that viral reactivation or enhancement of replication takes place after a transplant, due to the significantly immunocompromised nature of the patient immediately post-transplant. Reactivation typically takes place within 2-8 weeks following the transplant. Post-transplant infections have been documented in a wide variety of transplant patients, including both solid organ and hematopoietic stem cell transplant (HSCT) patients. The incidence of HHV-7 infections post liver transplantation has been reported to be as high as 45%.
The role of HHV-7 in transplant patients is not clearly defined, although there is mounting evidence that the effects of HHV-6 and HHV-7 reactivation in transplant patients may be mediated by their interaction with CMV. Co-infection with these three viruses is being evaluated on an ongoing basis to fully define their roles in predisposing transplant patients to illnesses caused by CMV infections. HHV-7 may also facilitate other opportunistic infections, such as fungal infections. Some studies have linked reactivation of HHV-7 with episodes of acute rejection.
HUMAN HERPES VIRUS 7 LABORATORY DIAGNOSIS
Serology is not a useful diagnostic tool because of the high prevalence of HHV-7 in the population. HHV-7 can be cultured in specialized diagnostic virology laboratories, however, due to the appearance of HHV-7 infection as a possible precursor to CMV reactivation, a more timely and sensitive method of diagnosis is warranted. Quantitative real-time PCR testing is a rapid and sensitive alternative to culture for HHV-7; allowing for monitoring of overall viral burden (viral load) and can be used to monitor the infection over time and the response to intervention.
HUMAN HERPES VIRUS 7 TREATMENT
There is little data available regarding the use of antiviral drugs to prevent or treat HHV-7 infection post-transplantation. Some in vitro studies suggest that ganciclovir may have limited effectiveness.
Selected References
Caserta MT, Mock DJ, Dewhurst S. Human herpesvirus 6. Clin Infect Dis. 2001;(33):1-5.
Emery VC. Human herpesvirus 6 and 7 in solid organ transplant recipients. Clin Infect Dis. 2001;(32):1357-1360.
Griffiths PD, Clark DA, Emery VC. ß-Herpesviruses in transplant recipients. J Antimicrobial Chemo. 2000;(45):29-43.
Knipe D, Howley P. Fields Virology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.
Ljungman P. ß-Herpesvirus challenges in the transplant recipient. J Infect Dis. 2002;186(Suppl 1):S99-109.
Razonable RR, Paya CV. The impact of Human herpesvirus-6 and -7 infection on the outcome of liver transplantation. Liver Transplant. 2002;(8):651-658.
Stoeckle MY. Human herpesvirus 6 and Human herpesvirus 7. In: Mandell GL, Bennett JE, Dolin, eds. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. Vol 2. 4th ed. New York, NY: Churchill Livingstone; 1995:1377-1379.
PAO-08-0707 PCR tests are performed pursuant to a license agreement with Roche Molecular Systems, Inc.
2-3 ml separated from whole blood collected in EDTA (lavender top) tube.
Ship at ambient temperature Monday-Friday
Whole Blood
3-5 ml collected in EDTA (lavender top) tube. Do not freeze.
Ship at ambient temperature Monday-Friday
ImmuKnow®Specimens- Whole Blood
2-3 ml collected in a sodium heparin (green top) tube. Maintain temperature by shipping the specimen in 2 inch thick styrofoam with specimen surrounded by ambient temperature gel packs.
Ship ambient for priority overnight delivery Monday‐Friday
Specimen must arrive at ViraCor within 30 hours of collection.
Hepatitis Specimens- Whole Blood
7-10 ml in EDTA, ACD Solution A, or PPT sterile tube. Minimum specimen requirement is 2 ml plasma. Separate plasma from cells within 4 hours of collection and freeze. To remove plasma from cells, centrifuge at 1000 xg for 10-15 minutes. Do not clarify by filtration or further centrifugation. If specimen was collected in PPT tube, the entire tube can be frozen if desired following centrifugation.
Ship ambient or frozen
Monday-Friday
Body fluid other than blood or urine
Collect 2-3 ml in a sterile screw-cap tube.
Ship at ambient temperature Monday-Friday
Bone Marrow
1-2 ml, collected in an EDTA (lavender top) tube. Do not freeze.
Ship at ambient temperature Monday-Friday
Bronchial Lavage/Bronchial Wash
2-3 ml, collected in sterile screw-cap tube.
Ship at ambient temperature Monday-Friday
CSF
1-1.5 ml in sterile screw-cap tube. Freeze prior to shipment.
Ship on DRY ICE
Monday-Friday
Eye swab
Swab the inflamed conjunctiva or corneal lesions. Place swab in 1-2 ml sterile saline or viral transport media in sterile screw-cap tube.
Ship at ambient temperature Monday-Friday
Fecal
Sterile swab (plastic shaft only) or very small (pea size) fecal sample placed in 1-2 ml sterile saline or viral transport in sterile screw-cap tube.
Ship at ambient temperature Monday-Friday
Nasopharyngeal Aspirate/Tracheal Aspirate
2-3 ml collected in sterile saline in sterile screw-cap tube.
Ship at ambient temperature Monday-Friday
Nasopharyngeal Swab
Sterile swab (flexible shaft) placed in 1-2 sterile saline or viral transport media in sterile screw-cap tube. Do not use calcium alginate swab.
Ship at ambient temerpature Monday-Friday
Swab
Sterile swab (plastic shaft only) placed in 1-2 ml sterile saline or viral transport media in sterile screw-cap tube. Do not use calcium alginate swab.
Ship at ambient temperature Monday-Friday
Tissue
Place in a sterile screw-top container, add a small amount of saline to keep moist.
Ship at ambient temperature Monday-Friday Frozen tissue is acceptable
Urine
5 ml sample collected in a sterile urinalysis container. Transfer to a 15 ml sterile screw-cap tube for shipment.
Ship at ambient temperature Monday-Friday
Vesicular Lesion
Collect fluid and cellular material from the base of several fresh vesicles. Place swab in 1-2 mil sterile saline or viral transport media in sterile screw-cap tube. Do not use calcium alginate swab.
Ship at ambient temperature Monday-Friday
Other Specimen
Please inquire.
Shipping
All specimens must be labeled with patient's name and collection date.
A ViraCor Test Request Form must accompany each specimen.
Ship specimens FedEx Priority Overnight to: ViraCor Laboratories | 1001 NW Technology Dr | Lee's Summit MO 64086
PCR tests are performed pursuant to a license agreement with Roche Molecular Systems Inc.
ImmuKnow is a registered trademark of Cylex Incorporated.
Respiratory Viral Panel is a product of Luminex Corporation.
Abstracts & Publications
Caserta MT, Mock DJ, Dewhurst S. Human herpesvirus 6. Clin Infect Dis. 2001;(33):1-5.
The development of techniques for the culture of lymphoid cells and the isolation of viruses that infect these cells led to the discovery of human herpesvirus (HHV) 6 in 1986. At the time, HHV-6 was the first new human herpesvirus to be discovered in roughly a quarter of a century, and its isolation marked the beginning of an era of discovery in herpesvirology, with the identification of HHV-7 and HHV-8 (Kaposi's sarcoma-associated herpesvirus) during the following decade. Like most human herpesviruses, HHV-6 is ubiquitous and capable of establishing a lifelong, latent infection of its host. HHV-6 is particularly efficient at infecting infants and young children, and primary infection with the virus is associated with roseola infantum (exanthem subitum) and, most commonly, an undifferentiated febrile illness. Viral reactivation in the immunocompromised host has been linked to a variety of diseases, including encephalitis, and HHV-6 has been tentatively associated with multiple sclerosis. This article discusses the major properties of HHV-6, its association with human disease, and the pathobiological significance of viral reactivation.
Emery VC. Human herpesvirus 6 and 7 in solid organ transplant recipients. Clin Infect Dis. 2001;(32):1357-1360.
The impact of cytomegalovirus, a member of the B-herpesvirus subgroup of the Herpesviridae, on patients who have undergone transplantation cannot be overstated. However, in the last 15 years, 2 additional members of the human
B-herpesvirus family have been discovered: human herpesvirus 6 and 7 (HHV-6 and HHV-7). The impact of HHV-6 and HHV-7 is assessed, as is the well-being of transplant recipients. Also discussed is whether the data on the pathological consequences of infection warrant routine screening for these viruses in solid organ transplant recipients.
Griffiths PD, Clark DA, Emery VC. ß-herpesviruses in transplant recipients. J Antimicrob Chemother. 2000;(45):29-43.
The three betaherpesviruses known to infect humans are cytomegalovirus (CMV) and human herpesviruses 6 and 7 (HHV-6 and -7). All three viruses can infect opportunistically after organ transplantation. CMV causes a variety of end-organ diseases, including pneumonitis, hepatitis and gastrointestinal ulceration. Patients who develop overt CMV diseases have significantly higher CMV viral loads than infected patients without evidence of clinical disease. A high CMV viral load largely explains the previously described risk factors for the development of CMV disease, which include donor/recipient serostatus before transplant and viremia after transplant. CMV also causes some cases of allograft rejection, which can be prevented by antiviral prophylaxis. Application of similar quantitative methods for the study of HHV-6 and -7 have shown that HHV-6 and CMV are significantly and independently associated with biopsy-proven graft rejection after liver transplantation. The full clinicopathological significance of the betaherpesviruses may, thus, be greater than is currently appreciated.
Ljungman P. B-herpesvirus challenges in the transplant recipient. J Infect Dis. 2002;186(suppl 1):S99-109.
Cytomegalovirus (CMV) has major consequences after allogeneic stem cell and solid organ transplantation. CMV may cause significant morbidity and mortality, and monitoring to detect reactivation to reduce disease or management of end organ disease is associated with increased resource utilization. Two other members of the B-herpesvirus family, human herpesvirus (HHV) type 6 and HHV-7, are increasingly recognized as important pathogens in transplant recipients, either by direct infection (e.g., encephalitis, hepatitis, or pneumonitis) or via interaction with CMV. In addition to direct effects of CMV infection, such indirect effects as an increased risk for bacterial and fungal infections or impaired graft acceptance and function are important research topics. Diagnosis and treatment of CMV infection is currently more advanced than for HHV-6 and HHV-7.
Mendez JC, Dockrell DH, Espy MJ, et al. Human beta-herpesvirus interactions in solid organ transplant recipients. J Infect Dis. 2001;(183):179-184.
The replication of B-herpesviruses-cytomegalovirus (CMV), human herpesvirus (HHV)-6 and HHV-7-and their association with CMV disease and response to antiviral therapy were prospectively investigated in 33 liver transplant recipients not given antiviral prophylaxis. CMV, HHV-6, and HHV-7 DNA were detected within 8 weeks after transplantation in 70%, 33%, and 42% of the patients, respectively. The univariate association between CMV disease and the 3 B-herpesviruses was more significant by virus load quantification than by qualitative detection of DNA. This association with high levels of CMV, HHV-6, and HHV-7 (P<.001, .022, and .001, respectively) occurred mainly in CMV-seronegative recipients of transplants from CMV-seropositive donors. Antiviral therapy with ganciclovir (Gcv) reduced the load of CMV and HHV-6 and HHV-7. These results suggest that CMV disease in transplant recipients is related to the unique interaction of the B-herpesviruses and is ultimately reduced after intravenous Gcv treatment.
Razonable RR, Fanning C, Brown RA, et al. Selective reactivation of human herpesvirus 6 variant A occurs in critically ill immunocompetent hosts. J Infect Dis. 2002;(185):110-113.
Reactivation of human B-herpesvirus (cytomegalovirus [CMV], human herpesvirus [HHV]-6, and HHV-7) in nonimmunocompromised hosts is rare. Because these viruses are susceptible to reactivation by cytokines and stress-related mechanisms, the incidence of their reactivation was investigated among 120 patients during stress related to critical illness and compared with findings among 50 healthy volunteers. Human ?-herpesvirus DNA was found in 65% of critically ill patients (60% men; mean age, 63 years) who required admission to an intensive care unit for medical (40%) or surgical (53%) indications or trauma (7%). HHV-6 reactivation was higher in critically ill patients than in healthy volunteers (54/101 vs. 0/50; P=.001). All patients except 1 were confirmed as HHV-6 variant A (mean virus load 5066 copies/106 peripheral blood leukocytes). The reactivation of HHV-6A did not affect disease severity and outcome. No significant reactivation of HHV-7 or CMV was demonstrated among the critically ill patients. These findings contribute to the less-defined epidemiology of HHV-6A infection.
Razonable RR, Paya CV. The impact of human herpesvirus-6 and -7 infection on the outcome of liver transplantation. Liver Transplantation. 2002;(8):651-658.
Human herpesvirus (HHV)-6 and -7 are novel members of the B-herpesvirus family that maintain latency in the human host after primary infection. Reactivation from latency and/or increased degree of viral replication occurs during periods of immune dysfunction. The clinical effect of HHV-6 and HHV-7 reactivation in recipients of liver transplants is now being recognized. Clinical illnesses such as fever, rash, pneumonitis, encephalitis, hepatitis, and myelosuppression have been described in a number of anecdotal reports. Moreover, a growing body of evidence suggests that the more important effect of HHV-6 and HHV-7 reactivation on the outcomes of liver transplantation may be mediated indirectly by their interactions with the other B-herpesvirus-cytomegalovirus (CMV). Coinfection among these three B-herpesviruses in clinical syndromes that were classically ascribed to be solely caused by CMV has been shown and has raised substantial interest in the potential role of HHV-6 and HHV-7 as copathogens in the direct and indirect illnesses caused by CMV. This article reviews the current scientific data on the role and the magnitude of impact of HHV-6 and HHV-7 infection on the outcomes of liver transplantation.
HHV-7 is detectable in a variety of transplant settings, both HSCT and solid organ. Direct effects of HHV-7 include fever, rash, myelosuppression, encephalitis, and pneumonitis. Potentially more important are the indirect effects HHV-7 has on CMV disease, invasive fungal disease, and allograft dysfunction. ViraCor’s quantitative HHV-7 DNA PCR assay is used to detect the presence of the virus and track the course of infection.
