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Viruses. 2019 Nov 1;11(11). pii: E1012. doi: 10.3390/v11111012.

HIV-1 Envelope Glycoprotein Amino Acids Signatures Associated with Clade B Transmitted/Founder and Recent Viruses.

Author information

1
Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, Québec QC H3T 1J4, Canada. alexis.kafando@umontreal.ca.
2
Laboratoire de santé publique du Québec, Institut national de santé publique du Québec, Sainte-Anne-de-Bellevue, Québec QC H9X 3R5, Canada. christine.martineau@canada.ca.
3
Centre de recherche du centre hospitalier de l'Université de Montréal, Montréal, Québec QC H3T 1J4, Canada. mohamed.el.far.chum@ssss.gouv.qc.ca.
4
Laboratoire de santé publique du Québec, Institut national de santé publique du Québec, Sainte-Anne-de-Bellevue, Québec QC H9X 3R5, Canada. eric.fournier@inspq.qc.ca.
5
Laboratoire de santé publique du Québec, Institut national de santé publique du Québec, Sainte-Anne-de-Bellevue, Québec QC H9X 3R5, Canada. florence.doualla-bell@inspq.qc.ca.
6
Laboratoire de santé publique du Québec, Institut national de santé publique du Québec, Sainte-Anne-de-Bellevue, Québec QC H9X 3R5, Canada. bouchra.serhir@inspq.qc.ca.
7
Faculty of Science, Hasselt University, 3500 Hasselt, Belgium. kazienga_adama@yahoo.fr.
8
Département de médecine sociale et préventive, École de santé publique, Université de Montréal, Montréal QC H3T 1J4, Québec, Canada. ndongosangare@yahoo.fr.
9
Centre de recherche du centre hospitalier de l'Université de Montréal, Montréal, Québec QC H3T 1J4, Canada. syllmoh@yahoo.fr.
10
Centre de recherche du centre hospitalier de l'Université de Montréal, Montréal, Québec QC H3T 1J4, Canada. chamberland.annie@videotron.ca.
11
Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, Québec QC H3T 1J4, Canada. hugues.charest@inspq.qc.ca.
12
Laboratoire de santé publique du Québec, Institut national de santé publique du Québec, Sainte-Anne-de-Bellevue, Québec QC H9X 3R5, Canada. hugues.charest@inspq.qc.ca.
13
Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, Québec QC H3T 1J4, Canada. c.tremblay@umontreal.ca.
14
Laboratoire de santé publique du Québec, Institut national de santé publique du Québec, Sainte-Anne-de-Bellevue, Québec QC H9X 3R5, Canada. c.tremblay@umontreal.ca.
15
Centre de recherche du centre hospitalier de l'Université de Montréal, Montréal, Québec QC H3T 1J4, Canada. c.tremblay@umontreal.ca.

Abstract

BACKGROUND:

HIV-1 transmitted/founder viruses (TF) are selected during the acute phase of infection from a multitude of virions present during transmission. They possess the capacity to establish infection and viral dissemination in a new host. Deciphering the discrete genetic determinant of infectivity in their envelope may provide clues for vaccine design.

METHODS:

One hundred twenty-six clade B HIV-1 consensus envelope sequences from untreated acute and early infected individuals were compared to 105 sequences obtained from chronically infected individuals using next generation sequencing and molecular analyses.

RESULTS:

We identified an envelope amino acid signature associated with TF viruses. They are more likely to have an isoleucine (I) in position 841 instead of an arginine (R). This mutation of R to I (R841I) in the gp41 cytoplasmic tail (gp41CT), specifically in lentivirus lytic peptides segment 1 (LLP-1), is significantly enriched compared to chronic viruses (OR = 0.2, 95% CI (0.09, 0.44), p = 0.00001). Conversely, a mutation of lysine (K) to isoleucine (I) located in position six (K6I) of the envelope signal peptide was selected by chronic viruses and compared to TF (OR = 3.26, 95% CI (1.76-6.02), p = 0.0001).

CONCLUSIONS:

The highly conserved gp41 CT_ LLP-1 domain plays a major role in virus replication in mediating intracellular traffic and Env incorporation into virions in interacting with encoded matrix protein. The presence of an isoleucine in gp41 in the TF viruses' envelope may sustain its role in the successful establishment of infection during the acute stage.

KEYWORDS:

HIV-1; acute/early infection; amino acids; cytoplasmic domain; genetic signatures; lentivirus lytic peptide segment 1; recent viruses, envelope; signal peptide; transmitted/founder viruses

PMID:
31683782
DOI:
10.3390/v11111012
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