Histopathological detection of owl's eye inclusions is still specific for cytomegalovirus in the era of human herpesviruses 6 and 7

Cytomegalovirus (CMV) is an important cause of multiple organ dysfunction in the immunocompromised host. ¹ Patients can present with hepatitis, pneumonitis, ulceration of the oesophagus or colon, retinitis, or encephalitis. Organ involvement is routinely diagnosed by biopsy, with visualisation of owl's eye intranuclear inclusions in stained tissue sections. ^{2, 3}

CMV (human herpesvirus 5) is the prototype member of the β-herpesvirinae, a subfamily of the herpesviridae. ⁴ In 1986 and 1990, respectively, two new herpesviruses were described and allocated to the β-herpesvirinae on the basis of their strong genetic relatedness to CMV; these viruses are termed human herpesvirus 6 (HHV-6) ⁵ and HHV-7. ^{6, 7} HHV-6 and HHV-7 can each cause febrile illness in young children, including exanthem subitum, ^{8- 10} and case reports suggest that, like CMV, HHV-6 may cause end organ disease in the immunocompromised host. ¹¹ Other reports suggest that CMV associated disease might be increased in patients co-infected with HHV-7 ^{12, 13} or HHV-6. ¹⁴ It is not known whether HHV-6 and/or HHV-7 can produce owl's eye inclusions in vivo but, if they do, this could complicate the interpretation of a postulated associated between these other viruses and CMV associated disease.

We have developed quantitative competitive polymerase chain reaction (QCPCR) methods to detect each of these three β-herpesviruses ^{15- 17} and quantify the viral load in biological samples, including tissue specimens. ¹⁸ In our study, we used these techniques to determine the sensitivity of histopathological visualisation of owl's eye inclusions to detect CMV infection and whether their presence is specific for CMV alone among the β-herpesvirinae.

Materials and methods

CLINICAL SAMPLES

To define the prevalence of CMV infection in patients with AIDS we prospectively collected multiple tissues from all such patients undergoing necropsies at this institution. For these clinicopathological studies, we aimed to collect up to 14 organs from each necropsy (lymph node, spleen, brain, lung, heart, kidney, adrenal, oesophagus, duodenum, colon, pancreas, liver, stomach, and salivary gland). A total of 139 organs were available from 11 unselected human immunodeficiency virus (HIV) positive patients (median, 14 organs/patient; range, 9-14). The median CD4 count at death was 10/mm ² (range, 0-20). Nine patients had been prescribed zidovudine during their illness but all died before protease inhibitor drugs became available. ¹⁹

HISTOPATHOLOGICAL EXAMINATION