TY - JOUR
T1 - The vertical transmission of human immunodeficiency virus type 1
T2 - Molecular and biological properties of the virus
AU - Ahmad, Nafees
N1 - Funding Information: The author thanks the National Institutes of Health (NIH/NIAID-AI40378, AI40378-06, NIH/FIC-TW01345) and the Arizona Disease Control Research Commission (ADCRC-9601, 7002, 8001) for funding the grants and the University of Arizona for providing the facilities, environment, and support that allowed the accomplishment of the work described in this review. Dr. Colombe Chappey, Virologic Inc., San Francisco, CA, and Nirav Merchant, University of Arizona Biotechnology Center, are acknowledged for assistance in nucleotide sequence analysis, Dr. Raymond C. Baker, Department of General Pediatrics, Children Hospital Medical Center, Cincinnati, OH, and Dr. Ziad M. Shehab, Department of Pediatrics, College of Medicine, University of Arizona, for providing HIV-1-infected mother-infant pairs’ samples, the AIDS Research and Reference Reagent Program for providing reagents, cell lines, and viral isolates, and Dr. John J. Marchalonis, Chairman, Department of Microbiology & Immunology, University of Arizona, for support, encouragement, and fruitful discussions. The author also thanks his past coworkers, Drs. Erik Matala, V.R.K. Yedavalli, Tobias Hahn, Mohammad Husain, Andrew Harodner and Katie Doktor, David Brooks, Scott Martin, Alison Holzer, and Kamlesh Patel, and current coworkers, Rajesh Ramakrishnan, Vasudha Sundaravardan, Roshni Mehta, Brian Wellenseik, Shailendra Saxena, and Tiffany Davis, for their contribution towards the ongoing research in the laboratory. Special thanks to Ms. Roshni Mehta for her assistance in the preparation of this manuscript.
PY - 2005/1
Y1 - 2005/1
N2 - The vertical (mother-to-infant) transmission of human immunodeficiency virus type 1 (HIV-1) occurs at an estimated rate of more than 30 % and is the major cause of AIDS in children. Numerous maternal parameters, including advanced clinical stages, low CD4+ lymphocyte counts, high viral load, immune response, and disease progression have been implicated in an increased risk of vertical transmission. While the use of antiretroviral therapy (ART) during pregnancy has been shown to reduce the risk of vertical transmission, selective transmission of ART-resistant mutants has also been documented. Elucidation of the molecular mechanisms of vertical transmission might provide relevant information for the development of effective strategies for prevention and treatment. By using HIV-1 infected mother-infant pairs as a transmitter- recipient model, the minor genotypes of HIV-1 with macrophage-tropic and non-syncytium-inducing phenotypes (R5 viruses) in infected mothers were found to be transmitted to their infants and were initially maintained in the infants with the same properties. In addition, the transmission of major and multiple genotypes has been suggested. Furthermore, HIV-1 sequences found in non-transmitting mothers (mothers who failed to transmit HIV-1 to their infants in the absence of ART) were less heterogeneous than those from transmitting mothers, suggesting that viral heterogeneity may play an important role in vertical transmission. In the analysis of other regions of the HIV-1 genome, we have shown a high conservation of intact and functional gag p17, vif, vpr, vpu, tat, and nef open reading frames following mother-to-infant transmission. Moreover, the accessory genes, vif and vpr, were less functionally conserved in the isolates of non-transmitting mothers than transmitting mothers and their infants. We, therefore, should target the properties of transmitted viruses to develop new and more effective strategies for the prevention and treatment of HIV-1 infection.
AB - The vertical (mother-to-infant) transmission of human immunodeficiency virus type 1 (HIV-1) occurs at an estimated rate of more than 30 % and is the major cause of AIDS in children. Numerous maternal parameters, including advanced clinical stages, low CD4+ lymphocyte counts, high viral load, immune response, and disease progression have been implicated in an increased risk of vertical transmission. While the use of antiretroviral therapy (ART) during pregnancy has been shown to reduce the risk of vertical transmission, selective transmission of ART-resistant mutants has also been documented. Elucidation of the molecular mechanisms of vertical transmission might provide relevant information for the development of effective strategies for prevention and treatment. By using HIV-1 infected mother-infant pairs as a transmitter- recipient model, the minor genotypes of HIV-1 with macrophage-tropic and non-syncytium-inducing phenotypes (R5 viruses) in infected mothers were found to be transmitted to their infants and were initially maintained in the infants with the same properties. In addition, the transmission of major and multiple genotypes has been suggested. Furthermore, HIV-1 sequences found in non-transmitting mothers (mothers who failed to transmit HIV-1 to their infants in the absence of ART) were less heterogeneous than those from transmitting mothers, suggesting that viral heterogeneity may play an important role in vertical transmission. In the analysis of other regions of the HIV-1 genome, we have shown a high conservation of intact and functional gag p17, vif, vpr, vpu, tat, and nef open reading frames following mother-to-infant transmission. Moreover, the accessory genes, vif and vpr, were less functionally conserved in the isolates of non-transmitting mothers than transmitting mothers and their infants. We, therefore, should target the properties of transmitted viruses to develop new and more effective strategies for the prevention and treatment of HIV-1 infection.
KW - AIDS
KW - Antiretroviral therapy
KW - HIV-1
KW - HIV-1 genes
KW - HIV-1 genotypes and phenotypes
KW - Vertical transmission
KW - Viral and host factors
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U2 - 10.1080/10408360490512520
DO - 10.1080/10408360490512520
M3 - Review article
C2 - 15697169
SN - 1040-8363
VL - 42
SP - 1
EP - 34
JO - Critical reviews in clinical laboratory sciences
JF - Critical reviews in clinical laboratory sciences
IS - 1
ER -