Dataset Information

An Alu Element Insertion in Intron 1 Results in Aberrant Alternative Splicing of APOBEC3G Pre-mRNA in Northern Pig-Tailed Macaques (Macaca leonina) That May Reduce APOBEC3G-Mediated Hypermutation Pressure on HIV-1.

ABSTRACT: APOBEC3 family members, particularly APOBEC3F and APOBEC3G, inhibit the replication and spread of various retroviruses by inducing hypermutation in newly synthesized viral DNA. Viral hypermutation by APOBEC3 is associated with viral evolution, viral transmission, and disease progression. In recent years, increasing attention has been paid to targeting APOBEC3G for AIDS therapy. Thus, a controllable model system using species such as macaques, which provide a relatively ideal in vivo system, is needed for the study of APOBEC3-related issues. To appropriately utilize this animal model for biomedical research, important differences between human and macaque APOBEC3s must be considered. In this study, we found that the ratio of APOBEC3G-mediated/APOBEC3-mediated HIV-1 hypermutation footprints was much lower in peripheral blood mononuclear cells (PBMCs) from northern pig-tailed macaques than in PBMCs from humans. Next, we identified a novel and conserved APOBEC3G pre-mRNA alternative splicing pattern in macaques, which differed from that in humans and resulted from an Alu element insertion into macaque APOBEC3G gene intron 1. This alternative splicing pattern generating an aberrant APOBEC3G mRNA isoform may significantly dilute full-length APOBEC3G and reduce APOBEC3G-mediated hypermutation pressure on HIV-1 in northern pig-tailed macaques, which was supported by the elimination of other possibilities accounting for this hypermutation difference between the two hosts.IMPORTANCE APOBEC3 family members, particularly APOBEC3F and APOBEC3G, are important cellular antiviral factors. Recently, more attention has been paid to targeting APOBEC3G for AIDS therapy. To appropriately utilize macaque animal models for the study of APOBEC3-related issues, it is important that the differences between human and macaque APOBEC3s are clarified. In this study, we identified a novel and conserved APOBEC3G pre-mRNA alternative splicing pattern in macaques, which differed from that in humans and which may reduce the APOBEC3G-mediated hypermutation pressure on HIV-1 in northern pig-tailed macaques (NPMs). Our work provides important information for the proper application of macaque animal models for APOBEC3-related issues in AIDS research and a better understanding of the biological functions of APOBEC3 proteins.

SUBMITTER: Zhang XL

PROVIDER: S-EPMC6997765 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

An Alu Element Insertion in Intron 1 Results in Aberrant Alternative Splicing of APOBEC3G Pre-mRNA in Northern Pig-Tailed Macaques (<i>Macaca leonina</i>) That May Reduce APOBEC3G-Mediated Hypermutation Pressure on HIV-1.

Zhang Xiao-Liang XL Luo Meng-Ting MT Song Jia-Hao JH Pang Wei W Zheng Yong-Tang YT

Journal of virology 20200131 4

APOBEC3 family members, particularly APOBEC3F and APOBEC3G, inhibit the replication and spread of various retroviruses by inducing hypermutation in newly synthesized viral DNA. Viral hypermutation by APOBEC3 is associated with viral evolution, viral transmission, and disease progression. In recent years, increasing attention has been paid to targeting APOBEC3G for AIDS therapy. Thus, a controllable model system using species such as macaques, which provide a relatively ideal <i>in vivo</i> syste ...[more]

PMID: 31776266

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Project description:BackgroundTuberculosis (TB) is a zoonotic disease that affects humans and domesticated and wild animals. Animals in zoos are potentially an important source of TB for humans; however they are often neglected in routine disease surveillance programs. This investigation reports an outbreak of TB in milu deer and northern pig-tailed macaques in a zoo in Wuhan, China, which highlighted the need for improved prevention and control of TB in China.MethodsBetween 24 November and 9 December 2020 two milu deer and a northern pig-tailed macaque that were displaying signs of wasting died. Post-mortem, histopathological diagnosis and acid fast staining were used for the dead animals. Multiple PCR for Mycobacterium tuberculosis complex (MTBC) was performed to identify the bacterial in both milu deer and northern pig-tailed macaque. The serum antibody iELISA for MTBC was then performed for all the surviving milu deer and northern pig-tailed macaques. Six seropositive milu deer and a seropositive northern pig-tailed macaque were subsequently euthanised and, along with two other dead milu deer, necropsied. DNA from these tissue samples was extracted and detected MTBC using PCR and Real-time PCR. Subsequently bacterial isolation was used to confirm the infection.ResultsThe lungs of the dead animals displayed gross and histological TB-like lesions and changes, and red staining bacilli were detected in smears of the lesions by microscopy after acid fast staining. Mycobacterium bovis (M. bovis) was detected in the two milu deer and Mycobacterium tuberculosis (M. tb) in the northern pig-tailed macaque using multiple PCR for MTBC. 35.3% surviving milu deer and 50% surviving northern pig-tailed macaques MTBC serologically positive. Six of the euthanised milu deer were also positive on a DNA test for M. bovis and the euthanised northern pig-tailed macaque was positive to M. tb.ConclusionsThis is the first report of tuberculosis in the endangered species, milu deer and northern pig-tailed macaques, in China, and warrants urgent attention by researchers and conservation authorities. These cases highlight the need for expanding surveillance for MTBC to zoos in China.

Dataset Information

An Alu Element Insertion in Intron 1 Results in Aberrant Alternative Splicing of APOBEC3G Pre-mRNA in Northern Pig-Tailed Macaques (Macaca leonina) That May Reduce APOBEC3G-Mediated Hypermutation Pressure on HIV-1.

Publications

An Alu Element Insertion in Intron 1 Results in Aberrant Alternative Splicing of APOBEC3G Pre-mRNA in Northern Pig-Tailed Macaques (<i>Macaca leonina</i>) That May Reduce APOBEC3G-Mediated Hypermutation Pressure on HIV-1.

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