Quantification of HTLV-I proviral load in experimentally infected rabbits.
BACKGROUND
Levels of proviral load in HTLV-1 infected patients correlate with clinical outcome and are reasonably prognostic. Adaptation of proviral load measurement techniques is examined here for use in an experimental rabbit model of HTLV-1 infection. Initial efforts sought to correlate proviral load with route and dose of inoculation and with clinical outcome in this model. These methods contribute to our continuing goal of using the model to test treatments that alleviate virus infection.


RESULTS
A real-time PCR assay was used to measure proviral load in blood and tissue samples from a series of rabbits infected using HTLV-1 inocula prepared as either cell-free virus particles, infected cells or blood, or by naked DNA injection. Proviral loads from asymptomatically infected rabbits showed levels corresponding to those reported for human patients with clinically silent HTLV-1 infections. Proviral load was comparably increased in 50% of experimentally infected rabbits that developed either spontaneous benign or malignant tumors while infected. Similarly elevated provirus was found in organs of rabbits with experimentally induced acute leukemia/lymphoma-like disease. Levels of provirus in organs taken at necropsy varied widely suggesting that reservoirs of infections exist in non-lymphoid organs not traditionally thought to be targets for HTLV-1.


CONCLUSIONS
Proviral load measurement is a valuable enhancement to the rabbit model for HTLV-1 infection providing a metric to monitor clinical status of the infected animals as well as a means for the testing of treatment to combat infection. In some cases proviral load in blood did not reflect organ proviral levels, revealing a limitation of this method for monitoring health status of HTLV-1 infected individuals.
Zhao
Tong-Mao
TM
Molecular and Cellular Immunogenetics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg #50, Room 5515, 50 South Drive, Bethesda, MD 20892, USA. tzhao@niaid.nih.gov
Hague
Bishop
B
Caudell
David L
DL
Simpson
R Mark
RM
Kindt
Thomas J
TJ
D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D015490:HTLV-I Infections / Q000821:virology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification*; D011817:Rabbits; D019562:Viral Load
D004279:DNA, Viral