Genetic and biological characterization of recombinant HIV type 1 with Env derived from long-term nonprogressor (LTNP) viruses.
Multiple factors are known to contribute to nonprogressive disease in long-term nonprogressors (LTNP). We previously selected LTNPs, in which broadly neutralizing antibodies against HIV-1 very likely contribute to disease prevention. Here, we characterize those LTNPs further. We analyzed sequences of the viral genes env, nef, vpr, tat, and rev as well as the cellular ccr5, HLA-B*5701, and HLA-B*27 genes derived from eight LTNPs, as mutations in these genes have been associated with the LTNP status in some studies. Furthermore, we compared the replication rates of recombinant reporter viruses carrying envelope proteins from LTNPs to control viruses from patients with similar CD4 count and viral load. Concerning the cellular factors, none of the eight LTNPs showed the 32-base pair deletion in the ccr5 gene, and HLA-B*5701 and HLA-B*27 alleles were detected in only one LTNP, respectively. The reading frames for the regulatory genes nef, vpr, tat, and rev were all open. Although Env sequences from LTNPs differed from those of control patients with respect to the length of variable domains and the number of N-glycosylation sites, these differences were not statistically significant and did not lead to differences in infectivity of recombinant reporter viruses.
Antoni
Sascha
S
Georg-Speyer-Haus, Institute for Biomedical Research, Frankfurt, Germany.
Walz
Nicole
N
Landersz
Margot
M
Humbert
Michael
M
Seidl
Christian
C
Dittmar
Matthias T
MT
Dietrich
Ursula
U
D002460:Cell Line; D015752:Genes, env / Q000235:genetics; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D020276:HIV Long-Term Survivors; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D019713:Receptors, CCR5 / Q000235:genetics; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics
D015235:HLA-B Antigens; D019713:Receptors, CCR5; D054311:nef Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus