Comparison of variable region 3 sequences of human immunodeficiency virus type 1 from infected children with the RNA and DNA sequences of the virus populations of their mothers.

Abstract

We have compared the variable region 3 sequences from 10 human immunodeSciency virus type 1 (H1V-1)-infected infants to virus sequences from the corresponding mothers. The sequences were derived from DNA of uncultured peripheral blood mononuclear cells (PBMC), DNA ofcultured PBMC, and RNA from serum collected at or shortly after delivery. The infected infants, in contrast to the mothers, harbored homogeneous virus populations. Comparison of sequences from the children and clones derived from DNA of the corresponding mothers showed that the transmitted virus represented either a minor or a major virus population of the mother. In contrast to an earlier study, we found no evidence of selection of minor virus variants during transmission. Furthermore, the transmitted virus variant did not show any characteristic molecular features. In some cases the transmitted virus was more related to the virus RNA population of the mother and in other cases it was more related to the virus DNA population. This suggests that either cell-free or cell-associated virus may be transmitted. These data will help AIDS researchers to understand the mechanism of transmission and to plan strategies for prevention of transmission.

Combination Treatment with Zidovudine, Didanosine, and Nevirapine in Infants with Human Immunodeficiency Virus Type 1 Infection

“…Coffin 21 has estimated that, on average, a mutation occurs several times daily at every position in the HIV-1 genome. Although minimal genotypic heterogeneity has been described in even highly variable regions (such as the V3 region of the envelope protein 22,23 ) of isolates obtained in early maternally acquired infection, our data suggest that by the age of two to three months diversification may have occurred to such a degree that mutations conferring resistance to antiretroviral drugs were present before therapy and were selected during therapy.…”

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

“…MTCT occurs in utero, during delivery, and through breastfeeding, at a rate of approximately 30% in the absence of antiretroviral therapy (6,19). Previous studies have demonstrated that, despite a complex viral population in the mother, only viruses of a restricted subset were typically transmitted to the infant (1,23,29,40,41,45,48). This suggests that some viruses may be favored for transmission in this setting.…”

Basal and Tat-transactivated expression from the human immunodeficiency virus type 1 long terminal repeat in human placental trophoblast rules out promoter-enhancer activation as the partial block to viral replication

“…In the context of this direction of viral spread, the villous syncytiotrophoblast-cytotrophoblast layer forming the maternal-fetal interface would be expected to play a critical role in modulating virus spread to the fetus. Recently, three different groups have used PCR to study possible HIV nucleotide sequence determinants common to viruses being transmitted to offspring (Wolinsky et al, 1992;Scarlatti et al, 1993;Mulder-Kampinga et al, 1993). All three studies reveal a homogeneous population of HIV-1 in the fetus and early neonate as compared with the mother, suggestive of a certain degree of selectivity of the transmission event, possibly during the first or Short communication Overall nucleotide sequence identity is 89 % between the two LTR fragments used in the reporter constructs.…”