In children, the mode of transmission is predominantly mother to child (vertical transmission) with transmission rate varying from 25% to 40%. The transmission can occur intrauterine (materno-fetal transfusion, placental inflammation), intrapartum (on exposure to body fluids and cervical secretions at the time of labour) and through breast-feeding. Infact transmission through breast-feeding has been reported to vary from 14% to 29% in various studies. The risk of in-utero transmission is approximately 10 %, the risk of intra-partum transmission, i.e. during labor and delivery, is approximately 155. Factors associated with rapid progression of HIV disease in vertically transmitted infants are:
· More advanced maternal disease
· In utero-infected infants
· High viral inoculum is related to rapid progression of the disease
Transmission of HIV by transfusion of blood and blood products is seen in patients with thalassemia and patients with Hemophilia or leukemia who require repeated transfusions.
In adults, HIV transmission usually occurs through sexual transmission through the mucosa of the lower genital tract or rectum.
Both free and cell-associated virions can enter the body, interact with Langerhans and dendritic cells which can internalize HIV and transmit the virus to CD4+ T cells. Reproduction of HIV in mucosal CD4+CCR5+ cells (memory T cells) occurs soon after infection, and rapidly spreads to local and distant sites.
How does HIV cause disease ?
HIV infection usually requires both CD4 and a chemokine receptor to infect target cells. Two major co-receptors have been identified, namely CCR5 and CXCR4 receptors. In general, CXCR4 receptors predominate on T-lymphocytes cells and CCR5 on cells of the macrophage cells. The predominant viral species within the individual early in infection is CCR5 tropic virus. Later, during disease progression, there appears to be a viral switch to predominant CXCR4, associated with more rapid progression of disease.
HIV at a cellular level
Following entry of the HIV virus into the human cell, viral genome is released in the cellular cytoplasm, conversion of viral RNA to viral DNA occurs which is undertaken by the viral enzyme, reverse transcriptase (RT). RT is not very efficient, and errors in production of a true complementary gene base from parental viral RNA leading to mutations in the viral DNA. The single strand complementary DNA is made into double stranded DNA by the viral polymerase and enters the cell nucleus for integration into the host cell genome. This is done by the integrase enzyme. Transcription of viral DNA to messenger RNA and genomic RNA is undertaken by host cell RNA polymerases. A large polyprotein is produced which is specifically cut by the viral protease enzyme.
References
1. Prendergast A, Klein N. The Immunology and Malignancy of Paediatric HIV. Available from Tr@inforPedHIV 2011.
2. Pillay D. Overview of HIV in children. Biology and patho-physiology of HIV infection file. Available from Tr@inforPedHIV 2011.
3. HIV- Wikipedia, the free encyclopedia. Available from URL: http://en.wikipedia.org/wiki/HIV. Accessed on 15th August 2011