The U.S. Principal Investigator, Dr. William Britt, and his German colleague, Dr. Mach, are studying effects of neutralizing antibodies on suppression or limitation of CMV infections. In normal individuals this agent causes limited viremia and virus spread because the cellular and humoral components of immunity are functional. In immunocompromised individuals, including organ transplant recipients and AIDS patients, CMV infections can become fulminant and fatal if, upon spread to the Central Nervous System, they produce encephalitis. In immune responsive individuals, humoral immunity may be inoperable, but only temporarily, if CMV variants arise which have mutated whereby preexisting, neutralizing antibodies fail to bind to the virus. Although further immune responses can eventually be evoked to suppress CMV variants in immune competent individuals, there are no such responses in AIDS patients. As an amplification of the parent grant, the foreign laboratory plans to study CMV variation in HIV-positive individuals who are severely immunocompromised. A second and related objective is to understand how changes in the virus antigen and responding neutralizing antibodies affect the clinical course of invasive, opportunistic infections (OI) by CMV. The two glycoprotein components on the virus gH and gB will be studied for nucleotide sequence changes and possible secondary effects on their glycosylation since these are the key virus surface structures combining with neutralizing antibodies. Special attention will be given to segments of gH, gB polypeptides known to be active in epitope recognition. More extensive surveys of CMV variants will be carried out by means of restriction endonuclease mapping to detect single-stranded conformational polymorphisms in gH and gB. The information obtained may reveal the extent of minimal changes which have to occur so as to alter protein conformation involved in antibody binding.
