Santos da Silva, E, Mulinge M, Lemaire M, Masquelier C, Beraud C, Rybicki A, Servais J-Y, Iserentant G, Schmit J-C, Seguin-Devaux C, Perez Bercoff D.  2016.  The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission., 2016. PloS one. 11(9):e0161596. Abstract

The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines.


Mulinge, M, Lemaire M, Servais J-Y, Rybicki A, Struck D, Santos da Silva E, Verhofstede C, Lie Y, Seguin-Devaux C, Schmit J-C, Perez Bercoff D.  2013.  HIV-1 tropism determination using a phenotypic Env recombinant viral assay highlights overestimation of CXCR4-usage by genotypic prediction algorithms for CRF01_AE and CRF02_AG [corrected]., 2013. PloS one. 8(5):e60566. Abstract

Human Immunodeficiency virus type-1 (HIV) entry into target cells involves binding of the viral envelope (Env) to CD4 and a coreceptor, mainly CCR5 or CXCR4. The only currently licensed HIV entry inhibitor, maraviroc, targets CCR5, and the presence of CXCX4-using strains must be excluded prior to treatment. Co-receptor usage can be assessed by phenotypic assays or through genotypic prediction. Here we compared the performance of a phenotypic Env-Recombinant Viral Assay (RVA) to the two most widely used genotypic prediction algorithms, Geno2Pheno[coreceptor] and webPSSM.

Santos da Silva, E, Mulinge M, Perez Bercoff D.  2013.  The frantic play of the concealed HIV envelope cytoplasmic tail., 2013 May 24. Retrovirology. 10:54. Abstract

Lentiviruses have unusually long envelope (Env) cytoplasmic tails, longer than those of other retroviruses. Whereas the Env ectodomain has received much attention, the gp41 cytoplasmic tail (gp41-CT) is one of the least studied parts of the virus. It displays relatively high conservation compared to the rest of Env. It has been long established that the gp41-CT interacts with the Gag precursor protein to ensure Env incorporation into the virion. The gp41-CT contains distinct motifs and domains that mediate both intensive Env intracellular trafficking and interactions with numerous cellular and viral proteins, optimizing viral infectivity. Although they are not fully understood, a multiplicity of interactions between the gp41-CT and cellular factors have been described over the last decade; these interactions illustrate how Env expression and incorporation into virions is a finely tuned process that has evolved to best exploit the host system with minimized genetic information. This review addresses the structure and topology of the gp41-CT of lentiviruses (mainly HIV and SIV), their domains and believed functions. It also considers the cellular and viral proteins that have been described to interact with the gp41-CT, with a particular focus on subtype-related polymorphisms.


Coddens, A, Verdonck F, Mulinge M, Goyvaerts E, Miry C, Goddeeris B, Duchateau L, Cox E.  2008.  The possibility of positive selection for both F18(+)Escherichia coli and stress resistant pigs opens new perspectives for pig breeding., 2008 Jan 01. Veterinary microbiology. 126(1-3):210-5. Abstract

F18(+)Escherichia coli infections causing post-weaning diarrhoea and/or oedema disease are a major cause of economic losses in pig industry. To date, no preventive strategy can protect pigs from F18(+)E. coli infections. One of the most attractive approaches to eliminate F18(+)E. coli infections is the selection for pigs that are resistant to F18(+)E. coli infections. However, this strategy was not believed to be favourable because of reports of genetic association with the stress-susceptibility gene in the Swiss Landrace. To investigate this potential association more thoroughly, 131 randomly selected Belgian hybrid pigs were genotyped for both the F18(+)E. coli resistance alleles (FUT1(A)) and the stress-susceptibility alleles (RYR1(T)) and their association was investigated by determining the linkage disequilibrium. This linkage disequilibrium (LD=-0.0149) is close to zero and does not differ significantly from 0 (likelihood ratio test chi(1)(2)=1.123, P=0.29), demonstrating no association between the FUT1(A) and RYR1(T) alleles. Furthermore, only a small fraction (4.6%) of the Belgian pigs was found to be resistant to F18(+)E. coli infections. Our results suggest that selection for F18(+)E. coli resistant pigs might be an attractive approach to prevent pigs from F18(+)E. coli infections, unlike to what has previously been postulated.

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