Near full-length clones and reference sequences for subtype C isolates of HIV type 1 from three different continents.

Among the major circulating HIV-1 subtypes, subtype C is the most prevalent. To generate full-length subtype C clones and sequences, we selected 13 primary (PBMC-derived) isolates from Zambia, India, Tanzania, South Africa, Brazil, and China, which were identified as subtype C by partial sequence analysis. Near full-length viral genomes were amplified by using a long PCR technique, sequenced in their entirety, and phylogenetically analyzed. Amino acid sequence analysis revealed 10.2, 6.3, and 17.3% diversity in predicted Gag, Pol, and Env protein sequences. Ten of 13 viruses were nonmosaic subtype C genomes, while all three isolates from China represented B/C recombinants. One of them was composed primarily of subtype C sequences with three small subtype B portions in gag, pol, and nef genes. Two others exhibited these same mosaic regions, but contained two additional subtype B portions at the gag/pol overlap and in the accessory gene region, suggesting ongoing B/C recombination in China. All subtype C genomes contained a prematurely truncated second exon of rev, but other previously proposed subtype C signatures, including three potential NF-kappa B-binding sites in the viral promoter-enhancer regions, were found in only a subset of these genomes.

Maternal periconceptional alcohol consumption and risk for orofacial clefts.

OBJECTIVE: To investigate whether periconceptional maternal alcohol consumption increased the risk of delivering infants with orofacial cleft phenotypes. DESIGN: Data were derived from a large population-based case control study of fetuses and infants among a cohort of California births from 1987 to 1989 (n = 548,844). Information concerning alcohol consumption was obtained by telephone interviews with mothers of 731 infants (84.7% of eligible) with orofacial clefts and of 734 (78.2%) infants in a nonmalformed control group. RESULTS: Thirty-nine percent of mothers in the case group and 42% of mothers in the control group reported that they consumed alcohol during the period 1 month before through 3 months after conception. Relative to nonconsumers, women who reported alcohol consumption (/=5 drinks per drinking occasion compared with those who did not, we observed increased risks for isolated (no other major congenital anomaly) cleft lip with or without cleft palate, odds ratio = 3.4 (95% confidence interval, 1.1 to 9.7); multiple cleft lip with or without cleft palate, odds ratio = 4.6 (1. 2 to 18.8); and "known syndrome" clefts, odds ratio = 6.9 (1.9 to 28. 6). Adjustment for maternal cigarette smoking, race, education, or vitamin use did not substantially change observed risks. CONCLUSION: We observed a lack of increased risks of clefts for relatively low quantities of maternal alcohol consumption and increased risks of clefts for higher quantities of maternal alcohol consumption.

Risk for neural tube defect-affected pregnancies among women of Mexican descent and white women in California.

OBJECTIVES: This study investigated a previously reported 50% or more increased risk for neural tube defect-affected pregnancies among Latina women compared with White women. METHODS: Data were derived from a population-based case-control study of fetuses and live-born infants with neural tube defects in a 1989-through-1991 California birth cohort. Interviews were conducted with mothers of 538 (88% of eligible) infants/fetuses with neural tube defects and mothers of 539 (88%) nonmalformed control infants. RESULTS: The risk for a neural tube defect-affected pregnancy was approximately twice as high among women of Mexican descent than among White women (odds ratio = 1.9, 95% confidence interval [CI] = 1.5, 2.8). The odds ratio for Mexico-born Mexican women compared with White women was 2.4 (95% CI = 1.7, 3.2), whereas the risk for US-born women of Mexican and other racial/ethnic descent was not substantially higher than that for Whites. The higher risk among Mexico-born Mexican women was not attributable to differences in numerous studied parental characteristics and exposures. CONCLUSIONS: Given that nearly 20% of all California births are to Mexico-born Mexican women, the increased risks observed are relevant to the population burden of neural tube defects.

Epidemiologic characteristics of phenotypically distinct neural tube defects among 0.7 million California births, 1983-1987.

Isolated neural tube defects (NTDs) appear to have different risk factors compared to nonisolated NTDs. To extend those observations, we explored routinely collected child and parental characteristics as possible risk factors among isolated versus nonisolated NTD cases, among high versus low spina bifida cases, and among open versus skin-covered spina bifida case. Fetuses and liveborn infants with anencephaly or spina bifida among the 1983-87 cohort of births and fetal deaths (n = 712,863) were ascertained by the California Birth Defects Monitoring Program. One hundred and ninety-three anencephalic cases and 272 spina bifida cases were compared to a random sample of 5,000 liveborn infants. Among anencephalic cases, 55% were livebirths and 85% were isolated. The proportion of males was similar to females across all subgroups. Increased risks were found for Hispanic whites, with risk estimates highest for nonisolated cases (odds ratio = 4.0, 95% confidence interval [1.5, 10.5]). Among spina bifida cases, 92% were livebirths, 81% isolated, 82% open, and 86% were low. More males were found among the group with isolated high open defects, and fewer males were found among the group of all closed defects. The proportion of males was similar to females in all other subgroups. Cases were more likely to be Hispanic with risks largest for high open defects (odds ratio = 2.9, [1.2,6.6]), particularly for nonisolated cases. This study provides some evidence that further classifications of NTDs may reveal subgroupings of cases with different etiologies.

Endemic human T cell lymphotropic virus type II infection among isolated Brazilian Amerindians.

Evidence for human T cell lymphotropic viruses (HTLV) was sought in sera and cells collected from adults in 13 isolated South and Central American Indian tribes. Serologic tests identified frequent HTLV-II-like reactivity among the Cayapo and Kraho tribes, who live 330 km apart in Central Brazil. Polymerase chain reaction analyses of viral DNA in cell pellet and plasma fractions confirmed the virus as HTLV-II. Both tribes speak Gé and, at the time of blood collection (1974), subsisted as hunter/gatherers and slash and burn agriculturalists. Further testing of plasma from Cayapo and Kraho of all ages revealed overall HTLV-II prevalence rates of 33.3% and 12.2%, respectively, with increasing prevalence associated with age and female gender. These data reveal for the first time a high prevalence of HTLV-II infection in remote South American Indians with little contact with non-Indians. Thus, HTLV-II is postulated to be an ancient human virus in the New World.

Segregation of human T cell lymphotropic virus type I and II infections by antibody reactivity to unique viral epitopes.

A recombinant protein of the human T cell lymphotropic virus type I (HTLV-I) gp46 outer membrane envelope, MTA-4 (residues 129-203), reacted by Western blot with sera from HTLV-I-infected individuals from the United States and Jamaica but not with 24 (10%) of 242 Japanese sera. A related gp46 recombinant protein, MTA-1 (residues 162-209), reacted with all 58 sera from HTLV-I-infected US and Jamaican individuals and 238 of 242 sera from infected Japanese (combined sensitivity of 99%). Neither recombinant showed reactivity to sera from HTLV-II-infected individuals or uninfected controls. The reactivity of recombinant proteins containing the region of HTLV-II gp46 analogous to MTA-1 was also evaluated by Western blot: GH2-K15 (residues 157-205) and GH2-K55 (residues 162-205) reacted with 88 (98%) and 89 (99%), respectively, of 90 sera from HTLV-II-infected individuals but not with sera from HTLV-I-infected individuals or uninfected controls. These recombinant proteins should permit the development of assays to unambiguously confirm and differentiate HTLV-I and HTLV-II infections.