4.3 Virus -Induced ALL Animal Models
AKR mice are susceptible to leukemia and murine leukemia
viruses(Mulv) have been widely
used to simulate human leukemia in susceptible mouse strains(Rein,
2011). In the 1950s, Dr. Charlotte Friend injected the MuLV supernatant
from the spleen suspension of leukemia-affected AKR mice into newborn
mice to induce leukemia in adult Swiss mice or DBA/2 mice and cause
serial transmission(Friend, 1957). Lymphoblastic leukemia and lymphoma
caused by retroviral insertion mutations can be used to characterize new
genes related to the occurrence of lymphoid leukemia by describing the
virus insertion sequence, and confirming misregulation of several Notch
signaling genes (Weiser et al., 2007).
Leukemia caused by C-type RNA tumor viruses or retroviruses is mostly
T-cell type. If the body’s control system is out of control, this tumor
virus can turn hematopoietic cells into leukemic cells under the action
of reverse transcriptase, resulting in adult T-cell leukemia. Bovine
leukemia virus (BLV) and human T-cell leukemia virus type 1 (HTLV-1)
make up a unique retrovirus family. Both viruses cause
lymphoproliferative disease, with BLV affecting the B-cell lineage and
HTLV-1 affecting the T-cell lineage(Aida, Murakami, Takahashi &
Takeshima, 2013). BLV can infect a variety of cell lines(Graves &
Ferrer, 1976) and spread to rats(Altanerova, Portetelle, Kettmann &
Altaner, 1989), pigs, goats and sheep(Mammerickx, Portetelle & Burny,
1981)artificially. It is estimated that HTLV-1 has infected 5 to 10
million people worldwide and is a causative agent in adult T-cell
leukemia/lymphoma (ATLL), as well as other inflammatory diseases(Gallo,
Willems & Hasegawa, 2016; Martin, Tagaya & Gallo, 2018; Sodré Barmpas
et al., 2019). Researchers injected HTLV-1-infected cell lines into NOG
mice intraperitoneally, and other groups were given IR-treated HTLV-1
donor cells. Studies have found that the expression of Tax oncoproteins
was up-regulated, and its relationship with Extracellular Vesicles (EVs)
had a potential role in continuation of Tax-mediated pathogenesis, and
ultimately promoted the development of ALL(Pinto et al., 2019). Tax
oncoprotein enhanced uncontrolled replication of T cells and cellular
genes (such as IL-2/IL-2R), disrupted DNA repair mechanisms, causes
genetic instability, inhibits apoptosis of infected cells, and
interferes with cell cycle checkpoints(Ahmadi Ghezeldasht et al., 2013;
Currer et al., 2012). In addition, the levels of CD4+and CD8+ T cells in peripheral blood were
significantly increased, indicating that HTLV-I infection in peripheral
blood may cause the virus to invade CD4+ and
CD8+ T cell populations, as well as cells of the
monocyte/macrophage cell line(Anderson et al., 2018; Knight, Macatonia,
Cruickshank, Rudge & Patterson, 1993). These models are helpful for the
identification and function of ALL-associated proto-oncogenes,
facilitating us to better understand the mechanisms of virus-induced
leukemia, helping to develop new strategies aimed at limiting virus
transmission, and playing a huge role in promoting the development of
virus-induced leukemia treatment strategies.
5.