The host's inherent viral limiting factor can act directly on retroviruses such as HIV-1, destroying the normal life cycle of the virus in order to limit the role of virus replication. The main factors found
retrovirus escant limiting factors are APOBEC3, TRIM5 alpha, TRIMCyp, ZAP, Tetherin, SAMHAD1 and Mx2.
host virus limiting factors have species-specific limitations for retrovirus replication, which is also an obstacle to building appropriate animal models, where TRIM5 alpha/TRIMCyp is critical in limiting HIV-1 infection in primates.
's study of viral limiting factors helps to clarify the molecular immune mechanism of HIV-1 replication, build suitable animal models of AIDS, and discover new targets and treatment strategies for AIDS drugs.
TRIMCyp is a particular viral limiting factor, which is selectively spliced by the CypA gene inserted into the TRIM5 gene base through reverse transcription.
found a total of 4 TRIMCyp gene fusion models in mammals, the Chinese Academy of Sciences Kunming Institute of Zoology animal models and human disease mechanism key laboratory Zheng Yongtang team found two of the TRIMCyp gene fusion models.
Zheng Yongtang's team found a new TRIMCyp fusion model in the only flat-top monkey in the old continent that could be infected with HIV-1, and proved that the fusion gene protein product could not limit HIV-1 infection and replication, thus clarifying the important molecular mechanism of flat-top monkey susceptibility to HIV-1, and creating the first HIV-1 infection model of Beiping top monkey (Liao et al,AIDS, 2007); Kuang et al, Retrovirology, 2009; Pang et al, Sci Bull, 2018).
in the of the new experimental animal tree, TRIMCyp, which has a collection of three important gene-producing patterns of gene repetition, reversal and exon recombination, also lost its restrictive function on viruses such as HIV-1, SIV and N-MLV, but the tree TRIMCyp produced new immune regulation functions (Mu et al, Moll Biovol, 2013).
chart: The limitability of the retrovirus escribp and TRIM5 alpha in the bear monkey.
(A-C) Bear Monkey trimcyp and TRIM5 alpha co-limit HIV-1 and lose the ability to limit N-MLV; (D) The combination of TrimCyp and TRIM5 alpha in the bear monkey, (E) the TRIM5 alpha mutant with weak combined ability with the bear monkey TRIMCyp does not provide a strong synergetic limiting HIV-1 effect; and (F) the "F) monkey TRIMCyp and TRIM5 alpha collaborative effect."
interesting, two alleles (Cao et al, Zoo Res, 2011) were also found in bear monkeys that belongto to the same continent.
, however, so far there have been no studies of trimCyp and TRIM5 alpha, where the combined effects of two alleles limit the ability and mechanism of virus replication.
, Zheng Yongtang discipline team studied the bear monkey TRIMCyp and TRIM5 alpha respective anti-viral ability spectrum, found that both can limit HIV-1 replication, and only TRIM5 alpha can limit N-MLV replication;
this phenomenon suggests that the common expression of the two different viruses has different coordination effects.
consistent with in vitro overexpression experiments, HIV-1 replicates significantly lower in in vitro blood mononucleocells in bear monkeys carrying TRIMCyp and TRIM5 alpha than in the peripheral blood mononucleosome serometers of bear monkeys carrying only TRIM5 alpha pure conjugation.
further studies have found that the synergistic restrictions of TRIMCyp and TRIM5 alpha on HIV-1 occur early in HIV-1 replication, i.e. in the early stages of the shelling or reverse transcription period.
the synergetic function depends on the combination of the two, and suppressing its spatial integration level will lead to a decrease in synergy.
because the TRIMCyp fusion gene originates from the TRIM5 alpha gene, the change in cellular antiviral ability caused by TRIMCyp production indicates that the host produces a change in the balance of the selected antiviral capacity under certain viral pressures.
at the same time, the co-expression of the co-expression of two alleles also provides a new strategy for HIV-1 animal models and gene therapy.
the above findings were published online in Science China Life Sciences, with Dan and Zhu Jiawu, phD students at Kunming Animal Institute, co-authors and researcher Zheng Yongtang as the authors of the paper.
the research is supported by funds from the Ministry of Science and Technology, the National Natural Science Foundation of China and the Chinese Academy of Sciences.