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The Detection Of Immu-serological Index Of The Northern Pig-tailed Macaque (Macaca Leonina) And Molecular Cloning And Anti-HIV-1 Activity Of Its APOBEC3 Family Genes

Posted on:2016-10-23Degree:MasterType:Thesis
Country:ChinaCandidate:X L ZhangFull Text:PDF
GTID:2284330470970709Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
With the further research on biomedicine, the importance of nonhuman primate models is increasing. NHPs remain the first or the only choice for investigating major human diseases including HIV/AIDS, measles, malaria, hepatitis, but also in the study of human cognition and brain diseases. In addition, the research data from NHPs experiments better ensure efficacy and security of clinical application. Monkeys of macaque species, including pig-tailed macaques (Macaca nemestrina group), rhesus macaques (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis), are widely used in biomedical research. Among them, the pig-tailed macaque is the only Old World monkey that is susceptible to HIV-1 infection and has been widely used in the study of the HIV/AIDS field and other fields, such as xeno-transplantation, neurophysiology cognitive behavioural studies and so on. Pig-tailed macaques have been split into three species:northern pig-tailed macaques (NPMs, M. leonina), southern pig-tailed macaques (M. nemestrina) and Mentawai macaques (M. pagensis). Understanding biological data of this species will aid in establishing animal models, the proper treatment and clinical diagnosis of this species. Though HIV-1 can infect the pig-tailed macaque, it encounters great impediments to replication in this host. This fact has limited the application of PTM animal model of HIV-1 infection in the fields of vaccines and drug testing. HIV-1 in vivo in NPM undergoes a high rate of G to A mutation, which is very higher than the rate of G to A spontaneous mutation, which indicates that APOBEC3 proteins may play an important role in restricting the replication in vivo of HIV-1 in NPM.We previously reported the reference values of blood chemistry and hematology of NPMs. But little is known about their normal levels of some basic immunological parameters, such as serum immunoglobulins, complements and CRP levels. In this study, we measured and analyzed the levels of serum IgG, IgM, IgA, C3, C4 and CRP of healthy captive NPMs in different age and gender groups. The results showed that serum IgA, IgM, C3 and C4 levels were not related with age (P>0.05), while serum IgG levels rose progressively with age (r=0.202;P=0.045). On the other hand, serum IgG, IgA, IgM and C3 levels were higher in females than males (P<0.05). In addition, serum C3 concentration were positively and strongly correlated with that of C4 (r=0.700; P<0.0001). We provide some basic serum immunoglobulin and complement data of captive northern pig-tailed macaque, which is important for breeding and application of this species in biomedical research. Further exploration of immunological data from northern pig-tailed macaques will promote this species more application in infectious diseases, immunology and other fields of biomedical research.In addition, we cloned APOBEC3A-APOBEC3H genes from NPMs and by BLAST found coding sequences of NPM A3A-A3H up to 99% identity of relevant sequences of A3POBECA-APOBEC3H form RMs and southern pig-tailed macaques. Lastly we analyze the anti-HIV-1 activity of the A3A-A3H genes. NPM APOBEC3G and APOBEC3F show the greatest anti-HIV-1 activity, however NPM A3A and A3C show no anti-HIV-1 activity. This study indicates NPM APOBEC3G and APOBEC3F may play a critical role in restricting HIV-1 replication in NPMs in vivo and provides valuable information for optimization of animal models of AIDS.
Keywords/Search Tags:northern pig-tailed macaque, animal model, immunoglobulin, complement, APOBEC3, HIV
PDF Full Text Request
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