Approximately 17% of the human genome is comprised of long interspersed nuclear 
element 1 (LINE-1, L1) non-LTR retrotransposons. L1 retrotransposition is known 
to be the cause of several genetic diseases, such as hemophilia A, Duchene 
muscular dystrophy, and so on. The L1 retroelements are also able to cause colon 
cancer, suggesting that L1 transposition could occur not only in germ cells, but 
also in somatic cells if innate immunity would not function appropriately. The 
mechanisms of L1 transposition restriction in the normal cells, however, are not 
fully defined. We here show that antiretroviral innate proteins, human APOBEC3 
(hA3) family members, from hA3A to hA3H, differentially reduce the level of L1 
retrotransposition that does not correlate either with antiviral activity 
against Vif-deficient HIV-1 and murine leukemia virus, or with patterns of 
subcellular localization. Importantly, hA3G protein inhibits L1 
retrotransposition, in striking contrast to the recent reports. Inhibitory 
effect of hA3 family members on L1 transposition might not be due to deaminase 
activity, but due to novel mechanism(s). Thus, we conclude that all hA3 proteins 
act to differentially suppress uncontrolled transposition of L1 elements.