Theresa Calvelli

Maternofetal transmission of human immunodeficiency virus-1: the role of antibodies to the V3 primary neutralizing domain.

ABSTRACT: The increase in the number of human immunodeficiency virus-1 (HIV-1)-infected children is a direct consequence of the heterosexual spread of the disease to women and the growing number of HIV-positive i.v. drug users. It is not known how the majority of infants born to HIV-1-infected women escape HIV-1 infection, and, for those infected, the timing of HIV-1 transmission has yet to be determined. In addition, the role of maternal antibodies in the prevention of HIV-1 transmission to the fetus is unclear. We have previously demonstrated a correlation between vertical transmission and the absence of high-affinity/avidity antibodies to a peptide, KRI-HIGPGRAFYT, which corresponds to a region of the primary neutralizing domain of the gp120 V3 loop of HIVMN (MN-PND). The present study examines the correlation between the presence of these high affinity antibodies in women completing a pregnancy or undergoing an elective abortion and the detection of HIV-1 infection in their aborted fetuses. In several instances, transmission occurred despite high-affinity antibodies to the MN-PND. We have, therefore, evaluated the reactivity of sera to different MN-PND variants. In one infant born to a mother with high-affinity/avidity antibodies to KRIHIGPGRAFYT (classic MN-PND), the infected baby developed antibodies to an MN-PND variant peptide against which his mother did not mount a humoral immune response during pregnancy. This finding indicates that fetal infection with MN-PND escape mutants arising during pregnancy may occur during a period when the mother is serologically negative.

Alterations in Human Fetal Hematopoiesis Are Associated with Maternal HIV Infection

ABSTRACT: In the majority of adult and pediatric patients with AIDS, hematologic abnormalities including leukopenia, anemia, and thrombocytopenia are commonly observed. In addition to these findings, changes in hematopoietic progenitor cells occur, including a reduction of multipotential-forming units, granulocyte-macrophages, macrophage as well as eosinophil colony-forming units, and bone marrow erythyroid burst-forming units. This study examined alterations in human fetal liver hematopoiesis in 2nd trimester abortuses from human immunodeficiency virus (HIV)-seropositive women. The differentiation and growth potential of hematopoietic cells in vitro were monitored. Upon initial isolation, some populations of liver hematopoietic cells from abortuses of HIV-sero-positive women were significantly decreased when compared to age-matched samples from fetuses of normal females including the percentage of early T cells [cluster of differentiation (CD)2], B cells (CD19), and early monocytes (CD14). A decrease in multipotent progenitors (CD34), myelomonocytes (CD33), and panleukocytes (CD45) was also observed. In contrast, after 21 d in culture, cells from HIV abortuses demonstrated an increase in the percentage of CD14 cells when stimulated with erythro-poietin and granulocyte-monocyte colony-stimulating factor, as well as an increase in CD45 phenotype after exposure to granulocyte-monocyte colony-stimulating factor alone. These samples showed a persistence of erythropoietic elements (transferrin and CD36 phenotype) when compared to normal controls. No significant difference in the in vitro growth of hematopoietic progenitors (bone marrow erythroid burst-forming units, granulocyte-macrophage colony-forming units, and multipotential forming units) between these samples and normal controls was found. These findings may be the result of transplacental hematopoietic inhibitors produced as a consequence of maternal HIV infection that result in similar hematologic abnormalities in AIDS patients.

Neopterin concentrations in pediatric human immunodeficiency virus infection as predictor of disease activity

Neopterin concentrations in 50 children with human immunodeficiency virus infection were correlated with disease course. The neopterin concentrations ranged from 4 to 70 nM with a mean of 34.7

A rapid test for the detection of human immunodeficiency virus antibodies in cord blood

25.1 (SD) nM compared with a mean of 6.1

Receptor-mediated maternofetal transfer of immunoglobulins. Inhibition of transport of anti-HIV-1 immunoglobulin by generic immunoglobulins in the in vitro perfused placenta.

1.6 nM in the human immunodeficiency virus-negative control group. Elevated neopterin concentrations above the upper range of the control group were detected as early as 5 months of age. Nineteen of 20 patients (95%) with neopterin concentrations above 20 nM either died or have severe clinical disease. Increasing neopterin concentrations were also associated with poor prognosis even though the first value was below 20 nM.

EFFECT OF IVIG ON CIRCULATING IMMUNE COMPLEXES (CIC) IN PEDIATRIC AIDS/ARC

The risk of infection by HIV-1 through transfusion of contaminated blood products has been markedly decreased but not eliminated by serological screening of donors. Methods are required to further minimize or eliminate the risk of infection of blood product recipients. We therefore examined the capacity of alkylureas to inhibit infectivity of HIV-1. Incubation of free HIV-1 virions with alkylureas suppressed their infectivity, and the minimal inhibitory concentration of the alkylureas was related to the length of the alkyl chain. Butylurea, the most potent inhibitor of HIV-1, inhibited the infectivity of 10(5) median tissue culture infective dose (TCID)50 of HIV-1, chronically HIV-1-infected H9 cells and mononuclear cells from two HIV-1-infected patients. Size fractionation of HIV-1 following incubation with butylurea indicated that the structure of the virus was disrupted by butylurea. This study demonstrates that butylurea, at a concentration that has been shown not to affect red blood cell function, can inhibit infectivity of extracellular and intracellular HIV-1. Since the HIV-1 inhibitory capacity of the alkylureas increases with the length of the alkyl side chain, it is likely that hydrophobic interactions between the alkylureas and HIV-1 are responsible for the observed effect.

1042 INTERFERONOPATHY IN THE BARE LYMPHOCYTE SYNDROME

A commercially available rapid test (HIVCHEK) was compared with an enzyme-linked immunosorbent assay (ELISA) for identifying human immunodeficiency virus type 1 in the serum of newborn infants. Of 1309 cord blood samples tested, the HIVCHEK test detected all the true-positive samples detected by ELISA. Of the 35 samples with positive ELISA results, six had negative results on Western blot; only 1 of the 30 samples with positive HIVCHEK results had negative results on Western blot. Thus the HIVCHEK test can be used to facilitate the rapid identification of HIV-1 in the serum of newborn infants.

Vertical transmission of human immunodeficiency virus is correlated with the absence of high-affinity/avidity maternal antibodies to the gp120 principal neutralizing domain.

The majority of children with acquired immunodeficiency syndrome (AIDS) exhibit signs of neurologic dysfunction. It is presently unclear whether the neuropathology of pediatric AIDS is the result of human immunodeficiency virus (HIV) infection of neural cells or the consequence of “bystander” pathogenic mechanisms. AIDS patients can have an array of neuropathologic abnormalities including perivascular inflammation, multinucleated giant cells, and microglial nodules. These findings support a pathogenic role for HIV-infected hematogenous cells invading the central nervous system (CNS) and causing “bystander” pathology. However, CNS tissue from AIDS patients can also show hypertrophy of oligodendrocyte nuclei, demyelination, gliosis, and disseminated necrotic foci, which suggests that neural cells may also be infected by HIV.