Structural Analysis of Merkel Cell Polyomavirus (MCPyV) Viral Capsid Protein 1 (VP1) in HIV-1 Infected Individuals
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Prezioso, Carla; Bianchi, Martina; Obregon, Francisco; Ciotti, Marco; Sarmati, Loredana; Andreoni, Massimo; Palamara, Anna Teresa; Pascarella, Stefano; Moens, Ugo; Pietropaolo, Valeria
Abstract
Merkel cell polyomavirus (MCPyV) viral protein 1 (VP1) is the capsid protein that mediates virus attachment to host cell receptors and is the major immune target. Given the limited data on MCPyV VP1 mutations, the VP1 genetic variability was examined in 100 plasma and 100 urine samples from 100 HIV+ individuals. Sequencing of VP1 DNA in 17 urine and 17 plasma specimens, simultaneously MCPyV DNA positive, revealed that 27 samples displayed sequences identical to VP1 of MCC350 strain. VP1 from two urine specimens had either Thr47Ser or Ile115Phe substitution, whereas VP1 of one plasma contained Asp69Val and Ser251Phe substitutions plus deletion ( increment ) of Tyr79. VP1 DNA in the remaining samples had mutations encoding truncated protein. Three-dimensional prediction models revealed that Asp69Val, Ser251Phe, and Ile115Phe caused neutral effects while Thr47Ser and Tyr79 increment produced a deleterious effect reducing VP1 stability. A549 cells infected with urine or plasma samples containing full-length VP1 variants with substitutions, sustained viral DNA replication and VP1 expression. Moreover, medium harvested from these cells was able to infect new A549 cells. In cells infected by samples with truncated VP1, MCPyV replication was hampered. In conclusion, MCPyV strains with unique mutations in the VP1 gene are circulating in HIV+ patients. These strains display altered replication efficiency compared to the MCC350 prototype strain in A549 cells.
AIDS incidence and survival in a hospital-based cohort of HIV-positive patients from Sao Paulo, Brazil: The role of IFN-lambda 4 polymorphisms
JOURNAL OF MEDICAL VIROLOGY
Authors: da Silva Prates, Gabriela; Malta, Fernanda M.; de Toledo Goncalves, Fernanda; Monteiro, Mariana A.; Fonseca, Luiz Augusto M.; R. Veiga, Ana Paula; M. C. Magri, Marcello; Duarte, Alberto J. S.; Casseb, Jorge; Assone, Tatiane
Abstract
Few studies have reported the prognosis of human immunodeficiency virus (HIV)-positive patients followed for a long time in Brazil, particularly those including pre and post-HAART eras. The polymorphisms of interferon (IFN)-lambda 4 have been postulated as possibly associated with the pathogenesis of HIV infection. The aim of this study was to describe the incidence and mortality from a cohort of HIV-positive patients as well as whether IFN-lambda 4 gene polymorphisms (SNP rs8099917 and SNP rs12979860) were associated with HIV/acquired immune deficiency syndrome (AIDS) progression. We followed 402 patients for up to 30 years; 347 of them began follow-up asymptomatic, without any AIDS-defining opportunistic disease and/or a lymphocytes T CD4+ count of 350 cells/mm(3)or lower. We determined the probability of the asymptomatic subjects to remain AIDS-free, and the risk of death for those entering the study already with an AIDS diagnosis, as well as for subjects developing AIDS during follow-up. We compared the prognosis of patients with two different polymorphisms for the genes encoding for IFN-lambda 4, variants rs8099917 and rs12979860. The follow-up time of the 347 asymptomatic-at-entry subjects was 3687 person-years. IFN-lambda 4 rs8099917 polymorphisms were not associated with AIDS progression, but IFN-lambda 4 rs12979860 wild type genotype (CC) was associated with higher mortality compared to CT and TT, with an increased probability of death from AIDS (P = .01). In conclusion, genetic variations in IFN-lambda 4 on rs12979860 polymorphisms in HIV-infected patients may drive mortality risk.