Abstract
Different animal models have been proposed to investigate the mechanisms of Human T-lymphotropic Virus (HTLV)-induced pathogenesis: rats, transgenic and NOD-SCID/γcnull (NOG) mice, rabbits, squirrel monkeys, baboons and macaques. These systems indeed provide useful information but have intrinsic limitations such as lack of disease relevance, species specificity or inadequate immune response. Another strategy based on a comparative virology approach is to characterize a related pathogen and to speculate on possible shared mechanisms. In this perspective, bovine leukemia virus (BLV), another member of the deltaretrovirus genus, is evolutionary related to HTLV-1. BLV induces lymphoproliferative disorders in ruminants providing useful information on the mechanisms of viral persistence, genetic determinants of pathogenesis and potential novel therapies.
Highlights
bovine leukemia virus (BLV) naturally infects cattle, zebu and water buffalo but can be experimentally transmitted to sheep, goats or alpaca (Vicugna pacos) [1,2,3]
The most prevalent clinical manifestation is a benign accumulation of infected B-lymphocytes called persistent lymphocytosis (PL) affecting about one-third of infected animals [4,5]
We evaluated the therapeutic effectiveness of a strategy based on the induction of viral gene expression using valproic acid (VPA), a lysine deacetylase inhibitor [41,42]
Summary
BLV naturally infects cattle, zebu and water buffalo but can be experimentally transmitted to sheep, goats or alpaca (Vicugna pacos) [1,2,3]. BBLLVV--aasssoocciaiatetedd ppaatthhooggeenneessisis tthhuuss sshhaarreess aa sseerriieess ooff featureess with HTLVV--11--iinndduucceedd AAdduulltt TT--cceelll LLeeuukkeemmiiaa ((AATTLLLL)) bbuutt ddooeess aappppaarreennttllyy nnoott iinncclluuddee nneeuurrooddeeggeenneerraattiivvee ddiisseeaasseess ssuucchh aass HHTTLLVV--AAsssoocciaiatetedd MMyyeeloloppaaththyy//TTrrooppiiccaall SSppaasstitcic PPaararappaareresissis(H(HAAMM//TTSSPP)) [9[9].]. It is assumed tthhaatt ccoonnssuummppttiioonn ooff rraaww mmiillkk froomm BLLVV--iinnffeecctteeddccaatttlleeiissnnoottaassssoocciiaatteeddwwiitthhaanniinnccrreeaasseeddrriisskkooff ccaanncceerr iinn hhuummaann,, aalltthhoouugghh tthhee lliinnkk ccaannnnoottbbeeffoorrmmaalllyyeexxcclluuddeedd[[1100]]. BLV microRNAs are transcribed from a region dispensable for in vivo infectivity but are abundantly expressed in leukemic B cells (about 40%) [21] This evidence contradicts the dogma that naturally occurring RNA viruses will not encode miRNAs to avoid unproductive cleavage of their genomes. These observations emphasize the dichotomy between conclusions drawn from in vitro experimentations and their relevance in the animal model
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