Autor(es):
Remédios, M. 
; Paixão, E. ; Feliciano, H. ; Silva-Graça, A. ; Pádua, E.
Data: 2010
Identificador Persistente: http://hdl.handle.net/10400.18/1564
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): HIV-2; nef; Longitudinal Variation; Infecções Sexualmente Transmissíveis
Descrição
Abstract publicado em: International Journal of Infectious Diseases. 2010;14(Supl 1). Background: Human Immunodeficiency Virus type 1 (HIV-1) and type 2 (HIV-2) may case a severe immunodeficiency in humans (AIDS). However HIV-2 is more frequently associated with lower levels of transmission and disease progression, compared with HIV-1 infections. The role of nef gene in vivo during the development of AIDS has been clearly demonstrated in simian immunodeficiency virus infected Rhesus macaques model, but the determinants which play a role in the pathogenesis of HIV are relatively poorly understood. However, even less is known about the role of nef in HIV-2 infections.
Methods: In this study, it was analyzed the variation of 48 nef gene sequences, obtained from samples taken between 1994 and 2009, corresponding to 17 HIV-2-infected individuals with different clinical stages of infection. The sequences obtained by Nested PCR were classified by phylogenetic analysis and the functional protein motifs, described as important in CD4 and MHC-I downregulation and in viral infectivity were also analyzed.
Results: In all individuals were identified nef sequences from group A of HIV-2, which encoded possible functional and complete protein. There was a greater conservation of residues in the Nef sequences of individuals in the symptomatic stage (63%), comparatively to individuals in the asymptomatic stage (19%). While some functional motifs (MGxxxS1, DDDD93, RR137 and DD205) and also residues (G128, I141 and L142) remained conserved, others (YSRF39, LRAR21, PxxP101, EE185) revealed changes during the follow-up period. The PxxP motif exhibited wide inter-individual variation in vivo from an HIV-1-like tetra-proline motif (PxxP)3 to disruption of the minimal core PxxPLR motif. The disruption was observed in 11 sequences exclusively from asymptomatic individuals (p=0.021). The sequence motif variation towards tetra-proline configuration was observed in 2 symptomatic individuals during time of infection. The results also revealed the existence of a negative selective pressure, as well as codons under positive pressure in the sequences.
Conclusion: In this HIV-2-infected individuals studied, it was observed a need for a greater degree of Nef protein conservation in a symptomatic phase. Sequences altered and potentially critical for the Nef function in vivo, in earlier stages of infection, may contribute at some level to a different pattern in viral pathogenesis and disease progression.
