- 作者: Tobias Hahn Rajesh Ramakrishnan Nafees Ahmad
- 作者服務機構: Department of Microbiology and Immunotogy, College of Medicine, The University of Arizona Health Sciences Center, Tucson, Ariz., USA
- 中文摘要: --
- 英文摘要: The nef gene is conserved among members of humanand simian immunodeficiency viruses and may play animportant role in viral pathogenesis. To determine theevolutionary dynamics and conservation of functionalityof the human immunodeficiency virus type 1 (HIV-1) nefgene during maternal-fetal transmission, we analyzednefsequences from seven mother-infant pairs followingperinatal transmission, including a mother with infectedtwin infants. The nefopen reading frame was maintainedin mother-infant isolates with a frequency of 86.2% fol-lowing vertical transmission. While there was alowdegree of viral heterogeneity and estimates of geneticdiversity and high population growth rates of nef se-quences from mother-infant isolates, the infants' nefsequences were slightly higher with respect to theseparameters compared with the mothers' sequences.Both the mothers' and infants' nefsequences were underpositive selection pressure, as determined by a newmethod of Nielsen and Yang [Genetics 148:929-936;1998]. Based on genetic distance and phylogeneticparameters, the epidemiologically linked nefsequencesfrom mother-infant pairs were closer to each other com-pared with epidemiologically unlinked sequences fromindividuals. The functional domains essential for Nefactivity, including membrane binding, CD4 and MHC-Idownmodulation, T cell activation and interaction withfactors of the cellular protein trafficking machinery, wereconserved in most of the sequences from mother-infantpairs. The maintenance of intact nefopen reading frameswith conserved functional domains and a low degree ofgenetic variability following vertical transmission sup-ports the notion that nef plays an important role in HIV-1infection and replication in mothers and their perinatallyinfected infants.
- 中文關鍵字: --
- 英文關鍵字: HIV-1. Vertical transmission. nef. Genetic diversity