Role of human cytomegalovirus genotype polymorphisms in AIDS patients with cytomegalovirus retinitis.
Although several host factors have been identified to influence the course of HCMV infection, it still remains unclear why in AIDS patients without highly active antiretroviral therapy human cytomegalovirus (HCMV) retinitis is one of the most common opportunistic infections, whereas in other immunosuppressed individuals it has a low incidence. It was suggested that HCMV glycoprotein B strains may be suitable as marker for virulence and HCMV retinitis. Moreover, UL144 ORF, a member of the TNF-α receptor superfamily, may play a crucial role in innate defences and adaptive immune response of HCMV infection. Furthermore, sequence analyses of HCMV genes UL128, UL130, and UL131A as major determinants of virus entry and replication in epithelial and other cell types were performed. To evaluate the association of sequence variability of depicted viral genes with HCMV retinitis and in vitro growth properties in retinal pigment epithelial cells (RPE) and human foreskin fibroblasts (HFF), we compared 14 HCMV isolates obtained from vitreous fluid and urine of AIDS patients with clinically proven HCMV retinitis. Isolates were analyzed by PCR cycle sequencing and phylogenetic analysis. In addition, sequences of HCMV strains AF1, U8, U11, VR1814, and its cell culture adapted derivates were included. Sequence analysis of gB yielded three genetic subtypes (gB type 1 (5 isolates), gB type 2 (12 isolates), and gB type 3 (5 Isolates)), whereas sequence analysis of UL144 showed a greater diversity (7 isolates type 1A, 2 isolates type 1C, 7 isolates type 2, and 3 isolates type 3). In contrast, the UL128, UL130, and UL131A genes of all low-passage isolates were highly conserved and showed no preferential clustering. Moreover, in HFF and RPE cells, all of our HCMV isolates replicated efficiently independently of their genetic subtype. In conclusion, beside a possible link between the gB subtype 2 and HCMV retinitis, our study found no direct evidence for a connection between UL144/UL128/UL130/UL131A genotypes and the incidence of HCMV retinitis in AIDS patients.
Institute of Medical Virology, Goethe University Hospital, Frankfurt am Main, Germany. ju.vogel@kinderkrebsstiftung-frankfurt.de
Jens-Uwe
JU
Vogel
Jürgen
J
Otte
Frank
F
Koch
Hermann
H
Gümbel
Hans Wilhelm
HW
Doerr
Jindrich
J
Cinatl
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000328:Adult; D002460:Cell Line; D002648:Child; D016000:Cluster Analysis; D003587:Cytomegalovirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D017726:Cytomegalovirus Retinitis / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014556:Urine / Q000821:virology; D014764:Viral Proteins / Q000235:genetics; D014822:Vitreous Body / Q000821:virology
D004279:DNA, Viral; D014764:Viral Proteins