| Human Endogenous Retroviruses(HERVs)are a type of endogenized retrovirus that results from the integration of exogenous retroviruses into the human genome and is vertically inherited according to Mendelian inheritance.Over millions of years of integration and evolution,elements or fragments of HERVs have occupied approximately 8%-10% of the human genome.Most HERV genes have become silenced due to mutations or deletions during the process of evolution.Normally expressed HERVs play important roles in human evolution,immune function regulation,and reproductive development.However,aberrant expression of HERVs may be closely associated with viral infections as well as the occurrence and progression of diseases such as cancer,neurological disorders,and autoimmune diseases.HIV-1(Human Immunodeficiency Virus Type 1)is an exogenous retrovirus.Both HIV-1 and HERVs belong to the retrovirus family,suggesting a possible common ancestor.Recent studies have found that HIV-1 infection leads to abnormal expression of a large number of HERVs,particularly the HERV-K(HML-2)family,and the presence of HERV-K provirus and antibodies in HIV-1-infected individuals.It is believed that the abnormal expression of HERVs following HIV-1 infection may be due to the similar gene structure or regulatory elements shared by HIV-1 and HERVs.Furthermore,some studies suggest that the transcriptional changes in HERVs induced by HIV-1 infection may depend on the activity of the HIV-1 Tat(Trans-activator of transcription)protein.After HIV-1 infection,its Tat protein interacts with the long terminal repeats(LTRs)of HERVs,affecting their transcription.Due to the lack of proofreading activity in HIV-1 reverse transcriptase,HIV-1exhibits rich genetic diversity.Currently,the most widespread HIV-1 group worldwide,HIV-1 M,consists of 10 subtypes(A-D,F-H,and J-L),132 circulating recombinant forms,and numerous unique recombinant strains.The HIV-1 epidemic in China differs significantly from that in Europe and the Americas.The prevalent HIV-1 strains in China are primarily CRF07＿BC(44%)and CRF01＿AE(31%),while a single subtype B accounts for over 90% in Europe and the Americas.Given the unique and diverse HIV-1 strain distribution in China,in this study,we performed transcriptome sequencing analysis to investigate the transcriptional changes of HERVs induced by HIV-1 IIIB strain(subtype B)and GX2005002 strain(CRF01＿AE recombinant strain)in infected T-cell lines.We also examined the impact of HIV-1 GX2005002 strain and NL4-3 strain(subtype B)Tat proteins on HERV transcription.By identifying HERV genes differentially expressed by HIV-1 strains of different subtypes and Tat proteins,we aim to explore the underlying connections between phenotypic variations caused by different HIV-1 strains and HERV activation.We validated the transcriptome sequencing data through q RT-PCR in HIV-1-infected cells and identified specific HERVs whose transcriptional changes are induced by HIV-1 infection and HIV-1 Tat protein expression.Furthermore,we verified the transcriptional status of HERVs in peripheral blood lymphocytes of individuals infected with HIV-1 subtype B and CRF01＿AE.By comparing the differentially expressed HERVs induced by the two strains and their Tat proteins,we aim to predict the associated functions and pathways.Additionally,we will identify common HERVs that undergo transcriptional changes in response to infection by both strains,in order to explore the role of HERVs in HIV-1infection.We found that in vitro HIV-1 infection altered the transcription levels of HERVs in T-cell lines,and the HERVs showing transcriptional changes induced by both subtype strains exhibited both differences and similarities.The research results revealed significant differences in transcription levels,molecular functions,and biological processes of activated HERVs following infection with different HIV-1 strains.Compared to uninfected MT2 cells,differential expression analysis of HERV loci genes induced by HIV-1 IIIb strain infection in MT2 cells showed enrichment of the most significant biological processes,cellular components,and molecular functions in glycosyl compound biosynthetic process,vacuolar lumen,and bile acid binding,respectively.On the other hand,differential expression analysis of HERV loci genes induced by HIV-1 GX2005002 strain infection in MT2 cells showed enrichment of the most significant biological processes,cellular components,and molecular functions in ribosome biogenesis,preribosome,and bile acid binding,respectively.Similarly,compared to uninfected Jurkat cells,differential expression analysis of HERV loci genes induced by HIV-1 IIIb strain infection in Jurkat cells showed enrichment of the most significant biological processes,cellular components,and molecular functions in plasma membrane organization,myosin filament,and G-protein coupled chemoattractant receptor activity,respectively.Conversely,differential expression analysis of HERV loci genes induced by HIV-1 GX2005002 strain infection in Jurkat cells showed enrichment of the most significant biological processes,cellular components,and molecular functions in activation of NF-kappa B-inducing kinase activity,external side of plasma membrane,and cytokine binding,respectively.Enrichment analysis of HERVs induced by HIV-1 Tat-mediated transcriptional changes revealed that GX2005002-Tat-induced HERVs showed significant enrichment in biological processes,cellular components,and molecular functions associated with the type I interferon signaling pathway,SCF ubiquitin ligase complex,and cytokine activity,respectively.On the other hand,NL4-3-Tat-induced HERVs exhibited significant enrichment in biological processes,cellular components,and molecular functions related to the regulation of viral life cycle,actin cytoskeleton,and chemorepellent activity,respectively.These findings provide insights into the disease processes and transmission characteristics induced by different HIV-1 strains.Additionally,combining transcriptome sequencing and q RT-PCR validation,we found that erv＿1585966 was upregulated in both in vitro infection cell line samples of the two strains and peripheral blood lymphocytes of individuals infected with the two strains.Functional enrichment analysis of this locus’ s gene suggested that it may play an essential role in the pathogenesis of HIV-1 infection,providing a new target for further research on the interaction between HIV-1 and HERVs in terms of prevention and control. |
