Original Article

Modern Pathology (2006) 19, 726–737. doi:10.1038/modpathol.3800584; published online 10 March 2006

Anatomical mapping of human herpesvirus reservoirs of infection

Tiansheng Chen1 and S David Hudnall1

1Department of Pathology and Laboratory Medicine, University of Texas Medical Branch, Galveston, TX, USA

Correspondence: Dr SD Hudnall, MD, Department of Pathology and Laboratory Medicine, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0741, USA. E-mail: shudnall@utmb.edu

Received 19 January 2006; Revised 12 February 2006; Accepted 16 February 2006; Published online 10 March 2006.

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Abstract

Following primary infection, all eight human herpesviruses persist lifelong in the human host. However, a mapping of all anatomic sites of human herpesvirus persistence is lacking. Fresh tissue specimens representing approximately 40 major anatomic sites from eight autopsies were screened using a recently developed real-time PCR method for detection of all eight human herpesviruses. Patients with evidence of active herpesvirus infection (herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), varicella-zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpesvirus 6 (HHV-6), herpesvirus 7 (HHV-7), and herpesvirus 8 (HHV-8)) at the time of death were excluded to avoid detection of widely disseminated infection. Despite this precaution, widespread HSV-1 positivity (with blood positivity) was detected in one case—an elderly male who died of cardiac arrest. In a middle-aged male with HIV-AIDS, HSV-1 was found in neural and pharyngeal tissues, skin, cartilage, bone, and urinary bladder, whereas in two other cases, HSV-1 was restricted to neural tissues. HSV-2 was detected in a single site, the anus, in the male with HIV-AIDS. VZV was detected only twice, once in the adrenal gland and once in the small intestine. CMV was detected in three cases, most commonly in nasal mucosa, trachea, thyroid, intestine, and liver. EBV was detected in all eight cases, especially in nasal mucosa, tonsil, spleen, lymph node, tongue, and intestine, but in only two of six whole-blood specimens. HHV-6, like EBV, was detected in all eight cases, most commonly in salivary glands, thyroid, stomach, intestines, liver, and pancreas. HHV-7, like EBV and HHV-6, was detected in all eight cases, most commonly in salivary glands, tonsil, lymph nodes, and bone marrow. HHV-8 was detected in only two sites (both lymph nodes) from two cases. Herpesviruses were detected in three of six whole-blood specimens, including HSV-1, EBV, HHV-6, and HHV-7. These results represent the most comprehensive mapping of herpesvirus tissue distribution in humans reported to date.

Keywords:

herpes simplex virus, varicella zoster virus, cytomegalovirus, Epstein–Barr virus, human herpesvirus 6, human herpesvirus 7, human herpesvirus 8