Parasites may exit immunocompromised northern pig-tailed macaques (Macaca leonina) infected with SIVmac239.

Parasites can increase infection rates and pathogenicity in immunocompromised human immunodeficiency virus (HIV) patients. However, in vitro studies and epidemiological investigations also suggest that parasites might escape immunocompromised hosts during HIV infection. Due to the lack of direct evidence from animal experiments, the effects of parasitic infections on immunocompromised hosts remain unclear. Here, we detected 14 different parasites in six northern pig-tailed macaques (NPMs) before or at the 50th week of simian immunodeficiency virus (SIV) infection by ELISA. The NPMs all carried parasites before viral injection. At the 50th week after viral injection, the individuals with negative results in parasitic detection (i.e., 08247 and 08287) were characterized as the Parasites Exit (PE) group, with the other individuals (i.e., 09203, 09211, 10205, and 10225) characterized as the Parasites Remain (PR) group. Compared with the PR group, the NPMs in the PE group showed higher viral loads, lower CD4+ T cells counts, and lower CD4/CD8 rates. Additionally, the PE group had higher immune activation and immune exhaustion of both CD4+ and CD8+ T cells. Pathological observation showed greater injury to the liver, cecum, colon, spleen, and mesenteric lymph nodes in the PE group. This study showed more seriously compromised immunity in the PE group, strongly indicating that parasites might exit an immunocompromised host.

[Relationship between the methylation and mutation of p53 gene and endemic arsenism caused by coal-burning].

OBJECTIVE: To explore the influence of arsenic pollution caused by coal-burning on methylation (promoter and exon 5) and mutation (exon 5) of human p53 gene, and to analyze the relationship between methylation, mutation and arsenism. METHODS: According to the diagnostic criteria of endemic arsenism, 112 patients with arsenism (including 38 mild cases, 43 moderate cases and 31 severe cases) were selected in the areas with endemic arsenism from Xingren, Guizhou province. Among the subjects, 43 cases were diagnosed by dermatopathological methods, and they were divided into non-cancerous group (24 cases) and cancerous group (19 cases). 90 controls were selected from the non-arsenic polluted areas. Under the principle of informed consent, blood samples were collected from individuals. The methylation of p53 gene in promoter region and exon 5 were detected by extinction enzyme-PCR, the mutation of p53 gene (exon 5) was detected by PCR-SSCP, PCR products cloning and sequencing technology. RESULTS: The positive rates of methylation of p53 gene in promoter region were 13.16% (5/38), 27.91% (12/43) and 45.16% (14/31) respectively among mild, moderate and severe arsenism group, which were obviously higher than the rates in the control group (1.11% (1/90), χ² values were 8.679, 23.690, 41.199, respectively, both P values < 0.017). The positive rates of methylation of p53 gene were 25.00% (6/24) and 63.16% (12/19) in non-cancerous and cancerous group respectively, which were obviously higher than those in the control group (1.11% (1/90), χ² values were 18.762, 57.497, respectively, both P values < 0.025). The positive rates of methylation of p53 gene (exon 5) were 55.26% (21/38), 51.16% (22/43) and 48.39% (15/31) respectively among mild, moderate and severe arsenism group, which were obviously lower than the rates in the control group (88.88% (80/90), χ² values were 18.151, 23.168, 22.420, respectively, both P values < 0.017). The positive rates of methylation of p53 gene (exon 5) were 54.17% (13/24) and 42.11% (8/19) in non-cancerous and cancerous group respectively, which were obviously lower than those in the control group (88.88% (80/90), χ² values were 15.201, 22.075, respectively, both P values < 0.025). The mutation rates of p53 gene (exon 5) were respectively 5.26% (2/38), 16.28% (7/43) and 25.81% (8/31) among mild, moderate and severe arsenism group; while the results in moderate and severe arsenism group were obviously higher than in the control group (0.00%, χ² values were 15.465, 24.870, respectively, both P values < 0.017). The positive rate of mutation of p53 gene (exon 5) were respectively 16.67% (4/24) and 31.58% (6/19) in non-cancerous and cancerous group, which were obviously higher than it in the control group (0.00%, χ² values were 15.545, 30.077, both P values < 0.025). The hypermethylation of p53 gene in promoter region was related with the mutation of p53 gene (exon 5) (coefficient of association was 0.294, P value < 0.05); and the hypomethylation of p53 gene (exon 5) was related with the its mutation (coefficient of association was 0.410, P value < 0.05). CONCLUSION: Arsenic pollution caused by coal-burning can cause the hypermethylation of p53 gene in promoter region, hypomethylation and mutation of p53 gene (exon 5), and the changes of methylation of p53 gene are related with its mutation and might be one of the important etiological factors of arsenic pathogenicity or carcinogenesis.