Development of a mouse model for human immunodeficiency virus type 1 (HIV-1) infection has advanced through the progressive identification of host cell factors required for HIV-1 replication. Murine cells lack HIV-1 receptor molecules, do not support efficient viral gene expression, and lack factors necessary for the assembly and release of virions. Many of these blocks have been described using mouse fibroblast cell lines. Here we identify a postentry block to HIV-1 infection in mouse T-cell lines that has not been detected in mouse fibroblasts. While murine fibroblastic lines are comparable to human T-cell lines in permissivity to HIV-1 transduction, infection of murine T cells is 100-fold less efficient. Virus entry occurs efficiently in murine T cells. However, reduced efficiency of the completion of reverse transcription and nuclear transfer of the viral preintegration complex are observed. Although this block has similarities to the restriction of murine retroviruses by Fv1, there is no correlation of HIV-1 susceptibility with cellular Fv1 genotypes. In addition, the block to HIV-1 infection in murine T-cell lines cannot be saturated by a high virus dose. Further studies of this newly identified block may lend insight into the early events of retroviral replication and reveal new targets for antiretroviral interventions.Murine cells are refractory to human immunodeficiency virus type 1 (HIV-1) replication at multiple stages of the viral life cycle. While this has allowed a finer inspection of the role of various host factors in HIV-1 replication, it has been an impediment to the development of a genetically modified mouse permissive to HIV-1 infection. A number of host factors have been identified that are indispensable for replication of HIV-1. Necessary factors absent in murine T cells include the human forms of the HIV-1 receptor and coreceptor molecules, CD4 and CCR5, whose murine orthologs do not support HIV-1 entry (10). In contrast, the murine form of CXCR4 can be utilized as a coreceptor by HIV-1 (7, 69). Postentry, human cyclin T1 is necessary for efficient Tat-mediated transactivation of the HIV-1 long terminal repeat (LTR) (22). Additional blocks in later steps of the HIV-1 life cycle in murine cells include excessive splicing of HIV-1 genomic RNA (49) and defects in Rev function (72). Aberrant splicing of HIV-1 mRNA appears to be partially corrected by the human splice inhibitor p32 (80). HIV-1 particle assembly is also impaired in murine cells (6,53). This restriction can be overcome by fusion of murine cells with human cells, suggesting that murine cells lack a factor (or factors) necessary for HIV-1 Gag assembly and release (52). Substitution of the HIV-1 matrix (MA) region with that of murine leukemia virus (MLV) also circumvents this block, supporting the notion that species-specific cofactors are critical for virion assembly and release (13,63).Not only do mouse cells lack some of the factors necessary for HIV-1 replication, they also express factors that actively interfere with retrovira...

Cross-species transmission of retroviruses poses a threat to mammalian species. Zoonoses have given rise to devastating diseases because the host organism is not prepared to resist a new pathogen. Mammals have developed several layers of defense against viruses, including an intracellular antiretroviral defense, a part of innate immunity. Retroviral restrictions had been studied for decades using murine leukemia virus in mice, however it has become clear that primates too have intrinsic mechanisms to ward off infections by retroviruses. Several of these antiretroviral restriction mechanisms have recently been identified, with two particularly well described factors being members of the tripartite motif (Trim) and APOBEC families. Both systems provide a strong barrier against lentiviral infections. The viruses have developed countermeasures that allow them to replicate despite the host factors. This review discusses our current knowledge of this ancient battle between mammalian hosts and their retroviral opponents.

The feline kidney cell line CrFK is used extensively for viral infectivity assays and for study of the biology of various retroviruses and derived vectors. We demonstrate the production of an endogenous, RD114-like, infectious retrovirus from CrFK cells. This virus also is shown to efficiently package Moloney murine leukemia virus vectors.

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