PMID- 37961113
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231214
DP  - 2023 Nov 2
TI  - Apobec-Mediated Retroviral Hypermutation In Vivo is Dependent on Mouse Strain.
LID - 2023.11.02.565355 [pii]
LID - 10.1101/2023.11.02.565355 [doi]
AB  - Replication of the complex retrovirus mouse mammary tumor virus (MMTV) is 
      antagonized by murine Apobec3 (mA3), a member of the Apobec family of cytidine 
      deaminases. We have shown that MMTV-encoded Rem protein inhibits proviral 
      mutagenesis by the Apobec enzyme, activation-induced cytidine deaminase (AID) 
      during viral replication in BALB/c mice. To further study the role of Rem in vivo 
      , we have infected C57BL/6 (B6) mice with a superantigen-independent 
      lymphomagenic strain of MMTV (TBLV-WT) or a mutant strain (TBLV-SD) that is 
      defective in Rem and its cleavage product Rem-CT. Unlike MMTV, TBLV induced 
      T-cell tumors in microMT mice, indicating that mature B cells, which express the 
      highest AID levels, are not required for TBLV replication. Compared to BALB/c, B6 
      mice were more susceptible to TBLV infection and tumorigenesis. The lack of Rem 
      expression accelerated B6 tumorigenesis at limiting doses compared to TBLV-WT in 
      either wild-type B6 or AID-deficient mice. However, unlike proviruses from BALB/c 
      mice, high-throughput sequencing indicated that proviral G-to-A or C-to-T changes 
      did not significantly differ in the presence and absence of Rem expression. Ex 
      vivo stimulation showed higher levels of mA3 relative to AID in B6 compared to 
      BALB/c splenocytes, but effects of agonists differed in the two strains. RNA-Seq 
      revealed increased transcripts related to growth factor and cytokine signaling in 
      TBLV-SD-induced tumors relative to those from TBLV-WT, consistent with a third 
      Rem function. Thus, Rem-mediated effects on tumorigenesis in B6 mice are 
      independent of Apobec-mediated proviral hypermutation.
FAU - Byun, Hyewon
AU  - Byun H
FAU - Singh, Gurvani B
AU  - Singh GB
FAU - Xu, Wendy Kaichun
AU  - Xu WK
FAU - Das, Poulami
AU  - Das P
FAU - Reyes, Alejandro
AU  - Reyes A
FAU - Battenhouse, Anna
AU  - Battenhouse A
FAU - Wylie, Dennis C
AU  - Wylie DC
FAU - Lozano, Mary M
AU  - Lozano MM
FAU - Dudley, Jaquelin P
AU  - Dudley JP
AUID- ORCID: 0000-0002-1581-1098
LA  - eng
GR  - R01 AI131660/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20231102
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10635078
EDAT- 2023/11/14 06:43
MHDA- 2023/11/14 06:44
PMCR- 2023/11/09
CRDT- 2023/11/14 03:52
PHST- 2023/11/14 06:44 [medline]
PHST- 2023/11/14 06:43 [pubmed]
PHST- 2023/11/14 03:52 [entrez]
PHST- 2023/11/09 00:00 [pmc-release]
AID - 2023.11.02.565355 [pii]
AID - 10.1101/2023.11.02.565355 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Nov 2:2023.11.02.565355. doi: 10.1101/2023.11.02.565355.