Human cytomegalovirus glycoprotein polymorphisms and increasing viral load in AIDS patients

Abstract

BackgroundMultiple strains infection of human cytomegalovirus (HCMV) was found to be correlated with increased viral load in immunodeficient patients. However, the pathogenic mechanism underlying this correlation remains unclear. To evaluate genetic polymorphisms of HCMV glycoprotein and their potential role in its viral load, HCMV glycoprotein B, N, and O (gB, gN and gO) genotypes was studied in the population of HCMV infected acquired immune deficiency syndrome (AIDS) patients. The association between glycoprotein polymorphisms and HCMV viral load was analyzed.MethodsThe genetic polymorphisms of glycoprotein from sera of 60 HCMV infected AIDS patients was investigated by multiplex nested PCR and sequencing. HCMV viral load was evaluated by quantitative PCR.ResultsgB1, gO1a, and gN4a were the predominant glycoprotein genotypes in HCMV infected AIDS patients and composed 86.96%, 78.8%, and 49.2%, respectively. Only gN4a genotype infection significantly increased viral load (P = 0.048). 71% (43/60) of HCMV infected AIDS patients were found to carry multiple HCMV strains infection. A novel potential linkage of gO1a/gN4a was identified from multiple HCMV infected patients. It was the most frequent occurrence, accounted for 51.5% in 33 patients with gO and gN genotypes infection. Furthermore, the gO1a/gN4a linkage was correlated to an increased viral load (P = 0.020).ConclusionThe gN4a correlates to higher level HCMV load in AIDS patients. Interestingly, a novel gO1a/gN4a linkage is identified from the patients with multiple HCMV strains infection and is also associated with an increased viral load. Therefore, the pathogenic mechanism underlying glycoprotein polymorphisms and interaction of variants should be analyzed further.

Analysis of the relationship between human cytomegalovirus DNA and gB-1 genotype in the saliva of HIV/AIDS patients with xerostomia and salivary flow rate

“…This finding is consistent with those of previous studies showed that gB1 was found to be the predominant glycoprotein genotype (86.96%) among HCMV-infected AIDS patients. 16 Similar results have been reported that the most frequent HCMV genotype was gB1 followed by other genotypes among organ transplant patients in Turkey. 33 However, other studies confirmed that gB3 and gB2 were the most prevalent genotypes in the sera of AIDS patients and HCMV-infected neonates and a high incidence of mixed infection with the gB1 and gB3 genotypes.…”

“…[12][13][14][15] The gB genotype distribution among HIV/AIDS patients has been extensively studied with varying results. [16][17][18] The responsibility of HCMV for a variety of diseases, including salivary gland dysfunction, with the most common symptom being xerostomia in HIV/AIDS patients, has been widely investigated. [19][20][21][22] Xerostomia is the subjective sensation of a dry mouth usually associated with low salivary flow rate (hyposalivation).…”

Human cytomegalovirus and Epstein-Barr virus infections, risk factors, and their influence on the liver function of patients with acute-on-chronic liver failure

“…Human cytomegalovirus (HCMV) is a β human herpesvirus with positive rates of antibodies of 50–100% [ 1 , 2 ]. Primary HCMV infection is often acquired during early childhood, and in later development stages, HCMV establishes lifelong latency or persistence within a person through cells of myeloid lineage [ 1 ] or granulocyte-monocyte lineage [ 3 ].…”

“…Primary HCMV infection is often acquired during early childhood, and in later development stages, HCMV establishes lifelong latency or persistence within a person through cells of myeloid lineage [ 1 ] or granulocyte-monocyte lineage [ 3 ]. However, reactivated or exogenous reinfection with HCMV may occur and may become a major viral cause of morbidity and mortality in immunocompromised patients, such as organ or haematopoietic stem cell transplant (HSCT) recipients [ 4 – 6 ] and patients with acquired immune deficiency syndrome (AIDS) [ 1 , 2 ].…”

“…Studies on HCMV have focused mostly on immunosuppressed individuals [ 2 , 4 , 5 ]. Studies on EBV have mostly examined patients with neoplastic disease [ 10 ] and post-transplant lymphoproliferative disorder following HSCT [ 5 , 11 , 12 ].…”