Downloaded from www.microbiologyresearch.org by IP: 54.70.40.11 On: Fri, 02 Aug 2019 20:46:29 Human immunodeficiency virus type 1 gp120 envelope characteristics associated with disease progression differ in family members infected with genetically similar viruses Elly Baan, 1 Rene ´ e M. van der Sluis, 1 Margreet E. Bakker, 1 Vincent Bekker, 2 Dasja Pajkrt, 2 Suzanne Jurriaans, 3 Taco W. Kuijpers, 2 Ben Berkhout, 1 Katja C. Wolthers, 3 William A. Paxton 1 and Georgios Pollakis 1 Correspondence Georgios Pollakis g.pollakis@amc.uva.nl Received 17 July 2012 Accepted 24 September 2012 1 Laboratory of Experimental Virology (LEV), Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands 2 Emma Children’s Hospital, Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands 3 Clinical Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands The human immunodeficiency virus type 1 (HIV-1) envelope protein provides the primary contact between the virus and host, and is the main target of the adaptive humoral immune response. The length of gp120 variable loops and the number of N-linked glycosylation events are key determinants for virus infectivity and immune escape, while the V3 loop overall positive charge is known to affect co-receptor tropism. We selected two families in which both parents and two children had been infected with HIV-1 for nearly 10 years, but who demonstrated variable parameters of disease progression. We analysed the gp120 envelope sequence and compared individuals that progressed to those that did not in order to decipher evolutionary alterations that are associated with disease progression when individuals are infected with genetically related virus strains. The analysis of the V3-positive charge demonstrated an association between higher V3-positive charges with disease progression. The ratio between the amino acid length and the number of potential N-linked glycosylation sites was also shown to be associated with disease progression with the healthier family members having a lower ratio. In conclusion in individuals initially infected with genetically linked virus strains the V3-positive charges and N-linked glycosylation are associated with HIV-1 disease progression and follow varied evolutionary paths for individuals with varied disease progression. INTRODUCTION Large differences have been described amongst humans in their susceptibility to infection with human immunodefi- ciency virus type 1 (HIV-1) as well as rates of disease progression. After infection some individuals progress slowly in their disease course (slow progressors/long-term non-progressors) (Buchbinder et al., 1994; Cao et al., 1995; Easterbrook, 1994; Le ´vy, 1993) some progress rapidly and develop disease in as little as 2–5 years (fast progressors) (Anzala et al., 1995), whilst a small minority show no progression over 20 years of infection (elite controllers) (Deeks & Walker, 2007). Many viral as well as host factors have been associated with this variation in viral transmission and disease progression (Morgan et al., 2002). One important host factor associated with both HIV-1 trans- mission and disease progression is the 32 bp deletion in the CCR5 co-receptor (CCR5D32) for HIV-1 (Liu et al., 1996). Individuals homozygous for the deletion are highly protected against infection, whilst individuals heterozygous for the deletion are not protected from infection, but disease progression is attenuated once infected (Huang et al., 1996). Other host factors involved with the chemokine/chemokine receptor (axis) have been associated with altered rates of HIV-1 disease progression (Paxton & Kang, 1998; Singh et al., 2003). Numerous allelic polymorphisms in genes involved in the adaptive immune recognition by T-cells, Journal of General Virology (2013), 94, 20–29 DOI 10.1099/vir.0.046185-0 20 046185 G 2013 SGM Printed in Great Britain