APOBEC3
proteins are important cellular factors that restrict
infection by a number of viruses, including human immunodeficiency virus type 1 (HIV-1). Previously, we found that the mouse APOBEC3 (mA3) restricts
infection by mouse mammary tumor virus (MMTV) in its natural host. Dendritic cells (DCs) are the first in vivo targets of MMTV
infection. In this study, we demonstrate that mA3 expressed in target cells restricts MMTV
infection in DCs ex vivo and in vivo. By comparing
infection of DCs from mA3(+/+) and mA3(-/-) mice with one-hit viruses, we show that mA3 expression in target cells blocked MMTV
infection at a postentry step and acted together with virion-packaged mA3 to inhibit
infection. Similar results were obtained upon
infection of mouse DCs with HIV-1 cores pseudotyped with
vesicular stomatitis virus G protein. In addition, treatment of cells or mice with
lipopolysaccharide (LPS) caused increased levels of mA3 expression and rendered them resistant to MMTV
infection.
Alpha interferon treatment had a similar effect. This LPS-induced resistance to
infection was seen only in mA3(+/+) mice and not in mA3(-/-) mice, arguing that mA3 is the major anti-MMTV restriction factor that is induced upon DC maturation. Thus, increasing the levels of this intrinsic antiretroviral factor in vivo can lead to increased levels of restriction because of higher levels of both cell-intrinsic as well as virion-packaged APOBEC3.