Abstract
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.
Abbreviations | ||
3TC | = | 3′-thiacytidine |
ACTG | = | AIDS Clinical Trials Group |
AIDS | = | Acquired immunodeficiency syndrome |
AP | = | Adaptor proteins |
ART | = | Antiretroviral therapy |
AZT | = | Azidothymidine |
CCR5 | = | Chemokine receptor, transmembrane G-like protein, coreceptor for entry of macrophage-tropic HIV-1 |
CMV | = | Cytomegalovirus |
CNS | = | Central nervous system |
CTL | = | Cytotoxic T lymphocyte |
CXCR4 | = | Chemokine receptor, transmembrane G-like protein, coreceptor for entry of T-lymphotropic HIV-1 |
EBV | = | Epstein-Baar virus |
env | = | Structural gene of HIV-1 |
gag | = | Structural gene of HIV-1 |
HAART | = | Highly active antiretroviral therapy |
HIV-1 | = | Human immunodeficiency virus type 1 |
HOS | = | Human osteosarcoma |
IL | = | Interleukin |
MDM | = | Monocyte-derived macrophages |
MT | = | Macrophage-tropic |
nef | = | Accessory gene of HIV-1 |
NSI | = | Non-syncytium-inducing |
PBMC | = | Peripheral blood mononuclear cells |
PCP | = | Pneumocystis carinii pneumonia |
PCR | = | Polymerase chain reaction |
pol | = | Structural gene of HIV-1 |
R5 virus | = | Minor genotype of HIV-1 with macrophage-tropic and non-syncytium inducing phenotype (NSI); HIV virus that uses the CCR5 coreceptor for infection |
rev | = | Regulatory gene of HIV-1 |
SIV | = | Simian immunodeficiency virus |
TAR | = | Transactivation response region |
tat | = | Regulatory gene of HIV-1 |
UNAIDS | = | United Nations Program on AIDS |
USAID | = | United States Agency for International Development |
vif | = | Accessory gene of HIV-1 |
vpr | = | Accessory gene of HIV-1 |
vpu | = | Accessory gene of HIV-1 |
X4 | = | T-lymphotropic virus; HIV virus that uses the CXCR4 coreceptor for infection. |
Abbreviations | ||
3TC | = | 3′-thiacytidine |
ACTG | = | AIDS Clinical Trials Group |
AIDS | = | Acquired immunodeficiency syndrome |
AP | = | Adaptor proteins |
ART | = | Antiretroviral therapy |
AZT | = | Azidothymidine |
CCR5 | = | Chemokine receptor, transmembrane G-like protein, coreceptor for entry of macrophage-tropic HIV-1 |
CMV | = | Cytomegalovirus |
CNS | = | Central nervous system |
CTL | = | Cytotoxic T lymphocyte |
CXCR4 | = | Chemokine receptor, transmembrane G-like protein, coreceptor for entry of T-lymphotropic HIV-1 |
EBV | = | Epstein-Baar virus |
env | = | Structural gene of HIV-1 |
gag | = | Structural gene of HIV-1 |
HAART | = | Highly active antiretroviral therapy |
HIV-1 | = | Human immunodeficiency virus type 1 |
HOS | = | Human osteosarcoma |
IL | = | Interleukin |
MDM | = | Monocyte-derived macrophages |
MT | = | Macrophage-tropic |
nef | = | Accessory gene of HIV-1 |
NSI | = | Non-syncytium-inducing |
PBMC | = | Peripheral blood mononuclear cells |
PCP | = | Pneumocystis carinii pneumonia |
PCR | = | Polymerase chain reaction |
pol | = | Structural gene of HIV-1 |
R5 virus | = | Minor genotype of HIV-1 with macrophage-tropic and non-syncytium inducing phenotype (NSI); HIV virus that uses the CCR5 coreceptor for infection |
rev | = | Regulatory gene of HIV-1 |
SIV | = | Simian immunodeficiency virus |
TAR | = | Transactivation response region |
tat | = | Regulatory gene of HIV-1 |
UNAIDS | = | United Nations Program on AIDS |
USAID | = | United States Agency for International Development |
vif | = | Accessory gene of HIV-1 |
vpr | = | Accessory gene of HIV-1 |
vpu | = | Accessory gene of HIV-1 |
X4 | = | T-lymphotropic virus; HIV virus that uses the CXCR4 coreceptor for infection. |