Subtle differences in selective pressures applied on the envelope gene of HIV-1 in pregnant versus non-pregnant women

• Published in: Infection, genetics and evolution genetics and evolution, 2018-08, Vol.62, p.141-150
• Main Authors: Ransy, Doris G., Lord, Etienne, Caty, Martine, Lapointe, Normand, Boucher, Marc, Diallo, Abdoulaye Baniré, Soudeyns, Hugo
• Format: Article
• Language: English
• Subjects: env Gene Products, Human Immunodeficiency Virus - genetics; Env protein; Evolution, Molecular; Female; HIV Infections - virology; HIV-1; HIV-1 - genetics; Humans; Models, Molecular; Pregnancy; Pregnancy Complications, Infectious - virology; Protein Conformation; Selection, Genetic; Selective pressure
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2018.04.020

Pregnancy is associated with modulations of maternal immunity that contribute to foeto-maternal tolerance. To understand whether and how these alterations impact antiviral immunity, a detailed cross-sectional analysis of selective pressures exerted on HIV-1 envelope amino-acid sequences was performed in a group of pregnant (n = 32) and non-pregnant (n = 44) HIV-infected women in absence of treatment with antiretroviral therapy (ART). Independent of HIV-1 subtype, p-distance, dN and dS were all strongly correlated with one another but were not significantly different in pregnant as compared to non-pregnant patients. Differential levels of selective pressure applied on different Env subdomains displayed similar yet non-identical patterns between the two groups, with pressure applied on C1 being significantly lower in constant regions C1 and C2 than in V1, V2, V3 and C3. To draw a general picture of the selection applied on the envelope and compensate for inter-individual variations, we performed a binomial test on selection frequency data pooled from pregnant and non-pregnant women. This analysis uncovered 42 positions, present in both groups, exhibiting statistically-significant frequency of selection that invariably mapped to the surface of the Env protein, with the great majority located within epitopes recognized by Env-specific antibodies or sites associated with the development of cross-reactive neutralizing activity. The median frequency of occurrence of positive selection per site was significantly lower in pregnant versus non-pregnant women. Furthermore, examination of the distribution of positively selected sites using a hypergeometric test revealed that only 2 positions (D137 and S142) significantly differed between the 2 groups. Taken together, these result indicate that pregnancy is associated with subtle yet distinctive changes in selective pressures exerted on the HIV-1 Env protein that are compatible with transient modulations of maternal immunity. •Overall diversity of the HIV-1 env gene did not differ between pregnant and non-pregnant women.•Selective pressure exerted on Env subdomains differed between the two groups.•All 42 positively selected sites mapped to the surface of the envelope protein.•Two positively selected sites differed significantly between the two groups.•Pregnancy-associated immune modulation could explain differences that were observed.