Glycoprotein B genotype correlates with cell tropism in vivo of human cytomegalovirus infection

Abstract

Human cytomegalovirus (HCMV) strains can be classified into four genotypes of the glycoprotein B (gB). In a previous study, the gB genotype 1 was found more frequently in bone marrow transplant recipients with nonfatal HCMV infection than in patients who died from HCMV disease [Fries et al. (1994): Journal of Infectious Diseases 169:769-774]. The distribution and cell tropism of different gB types in vivo were investigated. The gB type of HCMV was determined in blood or urine specimen from 76 organ and 47 bone marrow transplant recipients using PCR and restriction fragment length polymorphism (RFLP). The leukocyte populations (polymorphonuclear leukocytes, monocytes, T lymphocytes, non-T lymphocytes) of 20 viremic patients were purified by a fluorescence-activated cell sorter (FACS) and examined for HCMV infection by PCR. Sequence analysis of four randomly selected strains showed that gB types were similar to published sequences and no atypical gB types were found. Within the compartments blood and urine, the gB types were almost equally distributed, whereas the gB type 1, in contrast to gB types 2 and 3, did not infect T lymphocytes in vivo. These data show that the gB type correlates with viral tropism in vivo and thus provides further evidence that the gB variation may indeed influence the virulence of HCMV.

Genetic polymorphisms among human cytomegalovirus (HCMV) wild‐type strains

“…No linkage between gB types and severity and/ or outcome of HCMV disease in BMT subjects was shown in other studies [22,129,142].…”

“…This locus displays genetic polymorphism. Four main gB genotypes have been identified so far (gB-1, gB-2, gB-3 and gB-4) [19][20][21][22][23], although some rare non-prototypic variants have also been described (gB-5, gB-6 and gB-7) [24][25][26]. Peptide variation in gp116 was strongly clustered at precise regions of the protein (see Table 1 and Figure 1 for details).…”

“…HCMV virus strains can vary in virulence and differ in their tropism and 'pathogenic potential'. These differences seem to be related to genetic variability exhibited by 'key-genes' and detected among HCMV isolates [19,[21][22][23]94,95]. A substantial portion of the HCMV genome encodes proteins with the potential to affect virulence through immune evasion, molecular mimicry or interference with host chemokines [91,94,95].…”

“…A substantial portion of the HCMV genome encodes proteins with the potential to affect virulence through immune evasion, molecular mimicry or interference with host chemokines [91,94,95]. Potential virulence determinants can also be proteins that are important targets of the host immune response, such as envelope glycoproteins, whose genetic polymorphism could be associated with variability in the immune control of HCMV infection, as well as in the rate of infection, tissue tropism and fusion efficiency [13,22,28,51]. Although the effects of genomic variants on the biology of HCMV infection are largely unknown, molecular variations can help to study the epidemiology and pathogenesis of human cytomegalovirus.…”

Human cytomegalovirus genetic variability in strains isolated from Japanese children during 1983-2003

“…gB is a major component of the virion envelope and is transported to the plasma membrane of infected cells [Meyer-Konig et al, 1998a;Plotkin, 1999]. Chou and Dennison [1991] classified HCMV strains into four variant groups by PCR-RFLP.…”