Title

Effects of vpu start-codon mutations on human immunodeficiency virus type 1 replication in macrophages

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine

Date

9-18-2007

Document Type

Article

Medical Subject Headings

Cell Line; Cells, Cultured; Cloning, Molecular; Codon; Genome, Viral; HIV Core Protein p24; HIV-1; Human Immunodeficiency Virus Proteins; Humans; Kidney; Macrophages; *Polymorphism, Single Nucleotide; RNA-Directed DNA Polymerase; Restriction Mapping; Viral Envelope Proteins; Viral Regulatory and Accessory Proteins; Virus Replication

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

The human immunodeficiency virus type 1 (HIV-1) vpu protein increases the release of virus particles from infected cells. Mutations that abrogate vpu function have a profound effect on HIV-1 replication in primary macrophage cultures. About 1.24 % of primary isolates in the HIV databases have vpu start-codon mutations. In addition, the envelope of the AD8 isolate was reported to compensate for the lack of vpu, whilst the YU-2 virus (cloned directly from the brain tissue of an infected individual) is macrophage-tropic, despite having a vpu start-codon mutation. These observations raise the possibility that envelopes evolve to compensate for the loss of vpu function in vivo. Chimeric vpu+ and vpu- replication-competent clones were constructed that contained the envelopes of SF162, AD8 or YU-2. Macrophages were infected with these chimeras and virus release was measured over time by a reverse transcriptase ELISA. It was found that vpu-deficient chimeras carrying AD8 and YU-2 envelopes were consistently released at lower levels than their wild-type (wt) vpu counterparts, indicating that these envelopes did not compensate for the lack of vpu. Non-chimeric vpu+ and vpu- AD8 and YU-2 followed similar patterns, although replication by vpu-deficient AD8 was variable, with virion release reaching 60 % of that recorded for AD8 with a wt vpu. In summary, no evidence was found that the AD8 or YU-2 envelopes can compensate for the lack of vpu for replication in macrophages.

Rights and Permissions

Citation: J Gen Virol. 2007 Oct;88(Pt 10):2780-92. Link to article on publisher's site

Related Resources

Link to Article in PubMed