Gene defects clustered at the C-terminus of the vpr gene of HIV-1 in long-term nonprogressing mother and child pair: in vivo evolution of vpr quasispecies in blood and plasma.
Earlier studies on HIV-1 strains from HIV-1-infected long-term nonprogressors (LTNP) have reported that nef deletions and/or attenuations may be crucial in the survival of these patients. Other reports have suggested that the nef gene may not be the only gene involved, but attenuations in other accessory genes (vif, vpr, vpu), which play an important role in the viral life cycle, may be similarly important in chronic HIV-1 infection in LTNPs. Here we show the molecular and phylogenetic analyses of the vpr gene in HIV-1 strains derived from both blood and plasma of an HIV-1 infected long-surviving mother-child pair which has survived for > 13 years with HIV infection: both have maintained stable CD4+ T-cell counts. Analyses of blood-and plasma-derived HIV-1 vpr clones indicated the presence of defects (insertions and deletions) and length polymorphisms. Interestingly, all the vpr defects in PBMCs and plasma were clustered at the C-terminus of the Vpr protein, between amino acid residues 83 and 89, which has been implicated in the G2 cell cycle arrest as a step to early HIV-1 infection. In contrast, the vpr sequence analysis of HIV-1 strains derived from 30 different patients, who either died of AIDS-related illnesses or have AIDS, showed neither C-terminal defects nor length polymorphism in the vpr gene. Also, secondary structure predictions suggest that the naturally occurring mutations at the C-terminal region (aa 83-89) have the potential to affect the secondary structure of the Vpr protein. Also, in some cases, the out-of-frame mutations and the length polymorphisms affect the tat gene reading frame. Together, these mutations may have potential significance in conferring chronic HIV-1 infection in this long-surviving nonprogressing mother-child pair.
Wang
B
B
Department of Virology, Westmead Hospital, ICPMR, New South Wales, Sydney, Australia.
Ge
Y C
YC
Palasanthiran
P
P
Xiang
S H
SH
Ziegler
J
J
Dwyer
D E
DE
Randle
C
C
Dowton
D
D
Cunningham
A
A
Saksena
N K
NK
D000293:Adolescent; D000595:Amino Acid Sequence; D004279:DNA, Viral / Q000097:blood; D005260:Female; D016336:Gene Products, vpr / Q000737:chemistry / Q000235:genetics; D016334:Genes, vpr; D015658:HIV Infections / Q000097:blood / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D012367:RNA, Viral / Q000097:blood; D017741:Survivors; D054325:vpr Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D016336:Gene Products, vpr; D012367:RNA, Viral; D054325:vpr Gene Products, Human Immunodeficiency Virus