Effects of vpu start-codon mutations on human immunodeficiency virus type 1 replication in macrophages
dc.contributor.author | Richards, Kathryn H. | |
dc.contributor.author | Clapham, Paul R. | |
dc.date | 2022-08-11T08:08:57.000 | |
dc.date.accessioned | 2022-08-23T16:13:48Z | |
dc.date.available | 2022-08-23T16:13:48Z | |
dc.date.issued | 2007-09-18 | |
dc.date.submitted | 2008-09-11 | |
dc.identifier.citation | J Gen Virol. 2007 Oct;88(Pt 10):2780-92. <a href="http://dx.doi.org/10.1099/vir.0.83120-0">Link to article on publisher's site</a> | |
dc.identifier.issn | 0022-1317 (Print) | |
dc.identifier.doi | 10.1099/vir.0.83120-0 | |
dc.identifier.pmid | 17872532 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/33710 | |
dc.description.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. | |
dc.language.iso | en_US | |
dc.relation | <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17872532&dopt=Abstract">Link to Article in PubMed</a> | |
dc.relation.url | http://dx.doi.org/10.1099/vir.0.83120-0 | |
dc.subject | 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 | |
dc.subject | Life Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.title | Effects of vpu start-codon mutations on human immunodeficiency virus type 1 replication in macrophages | |
dc.type | Journal Article | |
dc.source.journaltitle | The Journal of general virology | |
dc.source.volume | 88 | |
dc.source.issue | Pt 10 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/gsbs_sp/373 | |
dc.identifier.contextkey | 626924 | |
html.description.abstract | <p>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.</p> | |
dc.identifier.submissionpath | gsbs_sp/373 | |
dc.contributor.department | Program in Molecular Medicine | |
dc.contributor.department | Graduate School of Biomedical Sciences | |
dc.source.pages | 2780-92 |