Chapter 23 – Cytomegalovirus Infections

Cytomegaloviruses (CMVs) comprise a group of agents in the herpesvirus family known for their ubiquitous distribution in humans and in numerous other mammals. In vivo and in vitro infections with CMVs are highly species specific and result in a characteristic cytopathology of greatly enlarged (cytomegalic) cells containing intranuclear and cytoplasmic inclusions. 1 The strikingly large, inclusion-bearing cells with a typical owl’s-eye appearance were first reported by Ribbert 2 in 1904 from the kidneys of a stillborn infant with congenital syphilis. Subsequently, Jesionek and Kiolemenoglou 3 reported similar findings for another stillborn infant with congenital syphilis. In 1907, Lowenstein 4 described inclusions in 4 of 30 parotid glands obtained from children 2 months to 2 years old. Goodpasture and Talbot 5 observed the similarity of these cells to the inclusion-bearing cells (giant cells) found in cutaneous lesions caused by varicella virus, and they postulated that cytomegaly was the result of a similar agent. The observation of a similar cytopathic effect after infection with herpes simplex virus led Lipschutz 6 and then others to suggest that these characteristic cellular changes were a specific reaction of the host to infection with a virus. The observation by Cole and Kuttner 7 that inclusion-bearing salivary glands from older guinea pigs were infectious for younger animals after being passed through a Berkefeld N filter in a highly species-specific manner led to the denomination of these agents as salivary gland viruses. The cellular changes observed in tissue sections from patients with a fatal infection led to the use of the term cytomegalic inclusion disease (CID) years before the causative agent was identified.