Perinatal infection by human immunodeficiency virus type 1 (HIV-1): relationship between proviral copy number in vivo, viral properties in vitro, and clinical outcome.
Human immunodeficiency virus type 1 (HIV-1) isolates from 25 perinatally HIV-1 infected children were classified according to their capacity to replicate in vitro as rapid (R), intermediate (S/R) and slow (S) variants. R-type viruses replicated on peripheral blood mononuclear cells (PBMCs) and grew better in T-lymphoid cells, even though 9 out of 12 isolates also maintained tropism for monocytoid cells. The S/R-type isolates replicated efficiently after several days of culture, while the S-type viruses displayed only a low and transient replication activity; however, both S/R- and S-type isolates exerted viral transactivation activity in an indicator monocytoid cell line. Replication patterns in vitro were significantly associated in vivo with the number of HIV-1 copies in PBMCs as determined by polymerase chain reaction: in children with R-type isolates, the number of HIV-1 proviral DNA molecules/10(5) PBMCs ranged from 62 to 571, and in children with S/R and S isolates the range was 5-43. Seven children had severe symptomatic HIV-1 infection, and in all an R-type virus was identified; 18 children had no or only mild symptoms, and among these, S-, S/R-, and R-type isolates were found in 5, 8, and 5 cases, respectively. Besides demonstrating HIV-1 variability in perinatal infection, these findings suggest that R-type virus might be a prerequisite for disease progression.
De Rossi
A
A
Institute of Oncology, Interuniversity Center for Cancer Research Padova, Italy.
Pasti
M
M
Mammano
F
F
Ometto
L
L
Giaquinto
C
C
Chieco-Bianchi
L
L
D002648:Child; D002675:Child, Preschool; D002999:Clone Cells; D005260:Female; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics / Q000382:microbiology* / Q000635:transmission; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000382:microbiology; D008431:Maternal-Fetal Exchange; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000382:microbiology*; D011379:Prognosis; D011533:Proviruses / Q000235:genetics / Q000472:pathogenicity*; D015533:Transcriptional Activation; D014779:Virus Replication