Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe mutants of human immunodeficiency virus type-1 (HIV-1) strain NL4-3, which are lacking the thirteenth, fifteenth, or seventeenth sites for N-linked glycosylation (g13, g15, g17) of the envelope protein gp120. All three sites are located within the hypervariable V3 loop region of gp120. Those mutants lacking carbohydrates g15 or combinations of g15/g17 showed markedly higher infectivity for GHOST cells (human osteosarcoma cells) expressing CXCR4 (GHOST-X4), compared to the fully glycosylated NL4-3 wild type virus. In addition, these mutants could also infect cells which exhibits low background expression of CXCR4, corresponding to <10% of that observed for GHOST-X4 cells. In addition to the enhanced infectivity observed, mutants lacking g15 and g17 showed increased resistance to inhibition by SDF-1, the natural ligand of CXCR4. Thus, loss of the oligosaccharides g15 and g17 in the V3 region of gp120 markedly influences CXCR4-specific infection.
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PMID:Loss of N-linked glycans in the V3-loop region of gp120 is correlated to an enhanced infectivity of HIV-1. 1118 57

The efficiency of the human immunodeficiency virus type-1 (HIV-1) to enter cells is defined primarily by amino acid exchanges in the external glycoprotein gp120 and in, especially its highly variable V3 loop region. To study entry efficiency of HIV-1 a competitive viral entry assay was developed, to be comprised of infectious virus as well as soluble gp120 (sgp120) as an entry competitor. Entry of viruses using the coreceptor CXCR4 was reduced by adding CXCR4-tropic sgp120 (X4-sgp120) SF2 or LAV expressed in the baculovirus system or by adding X4-sgp120 from NL-952 and NL-V3A virus mutants produced in a HeLa-P4 cell culture expression system. Adding X4-sgp120 into a CCR5-specific infection assay revealed that X4-sgp120 enhanced the infection of CCR5-tropic virus. Furthermore, the role of the V3 loop N-glycan g15 on entry efficiency was studied using virus mutants and sgp120 with different N-glycosylation and different coreceptor usage. These experiments showed that viral entry of R5-tropic viruses lacking the N-glycan g15 within the V3 loop was inhibited by CCR5-tropic sgp120 harboring the g15 N-glycan. Altogether, the data demonstrate that HIV-1 entry efficiency can be studied easily by using sgp120 as an internal control or by using autologous or heterologous sgp120-virus pairs.
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PMID:A virus-envelope paired competitive assay to study entry efficiency of human immunodeficiency virus type 1 in vitro. 2485 49