Affiliation:
1. Department of Biochemistry and Molecular Biology, Oregon Health Sciences University, Portland, Oregon 97201-3098
Abstract
ABSTRACT
The
vif
gene of human immunodeficiency virus type 1 (HIV-1) greatly enhances the infectivity of HIV-1 virions that are released from cells classified as nonpermissive (e.g., lymphocytes, macrophages, and H9 leukemic T cells) but is irrelevant in permissive cells (e.g., HeLa or COS cells). Recently, it was reported that
vif
expression in nonpermissive cells dramatically increases infectivity not only of HIV-1 but also of other enveloped viruses, including murine leukemia viruses (MLVs). This was surprising in part because MLVs and other murine retroviruses lack
vif
genes yet replicate efficiently in T lymphocytes. To investigate these issues, we first developed improved methods for producing substantial quantities of HIV-1 virions with
vif
deletions from healthy H9 cells. These virions had approximately the same amounts of major core proteins and envelope glycoproteins as the control wild-type virions but were only approximately 1% as infectious. We then produced H9 cells that contained wild-type or
vif
deletion HIV-
gpt
proviruses, which lack a functional
env
gene. After superinfection with either xenotropic or amphotropic MLVs, these cells released HIV-
gpt
virions pseudotyped with an MLV envelope plus replication-competent MLV. Interestingly, the pseudotyped HIV-
gpt
(
vif
deletion) virions were noninfectious, whereas the MLV virions simultaneously released from the same H9 cells were fully infectious. These results strongly suggest that the Vif protein functions in a manner that is both cell specific and at least substantially specific for HIV-1 and related lentiviruses. In addition, these results confirm that
vif
deletion HIV-1 virions from nonpermissive cells are blocked at a postpenetration stage of the infection pathway.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
27 articles.
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