Biochemistry
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- RETROVIRIDAE
- LIFE CYCLE OF THE RNA RETROVIRUS HIV
- CD4 count
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The negative sense ssRNA viruses share the following characteristics in common: -All are enveloped -All have virion associated polymerase -All have helical nucleocapsids -Odd bassl are the orthomyxoviruses because they are linear and their DNA is broken up into eight segments -Orthoymyxaviruses also replicated in both the nucleus and the cytoplasms. -Bunyaviruses are circular -Arenaviruses contain one negative sense and one antisense strandof RNA ’PAIN RESULTS FROM OUR BUNYONS ALWAYS -Paramyxoviruse, rhabdovirus, filovirus,orthomycovirus,bunyvirus, areneviruses RETROVIRIDAEImportant points about proteins in the HIV virus -GAG gene: p24 capsid-Structural proteins including capsid proteins, core nucleocapsid proteins, and matrix proteins that stabilizes the envelope -Pol Codes for RT which takes + sense RNA and turns it into DNA Integrase takes DNA made and integrates it into host DNA Protease: cleaves polyprotein (protease inhibitors work here) -Env gp120: surface protein that binds to the CD4 receptor in the host cell. Responsible for genetic drift gp 31: transmembrane protein for cellfusion -Vif Codes for infectivity -Nef Negative factor, down regulates -Tat Upregulates virus LIFE CYCLE OF THE RNA RETROVIRUS HIVHigh yield points from 174 -Virus attaches via gp 120 binding to CD4 receptor on the T helper cells -RNA taken into the cell and envelope is lost -RNA copied using the RT; Ds DNA with long terminal repeats is made -The DNA and integrase mirate into the nucleus and the DNA is integrates into the host DNA forming the provirus -Provirus remains in the host DNA -Rate of viral replication regualated b the activity of regulated proteins (tat/ref/nef) -Transcription produces ss (+) RNAs, some splced and some remain intact -Spliced RNAs will be used as mRNA -Whole RNA is used as genomic RNA -Translation produces the proteins, some of which are polyproteins that are cleaved by the protease -Assembly -Maturation and release -All protease inhibitors end in –AVIR -Triple treatment is two RT inhibitors and a protease inhbitor CDC CATEGORIES OF AIDS INFECTION
-Patients are asymptomatic when CD4 cell counts are in the range of 200-250 -Oral candidiasis is often the first manifestation (CDC category B) -Other category B infections include hairly leukoplakia -Idiopathic thrombocytic purpura -Listerosis -Pelvic inflammatory disease -Category C are AIDS defining conditions like HIV related encephalopathy, precurrent pneumonia, fungal infectons like esophageal candidiasis, invasive cervical carcinoma, systemic and disseminated fungal infections, recurrent salmonella septicemia. HIV DIAGNOSIS: -Screening done via ELISA. Tests for the antigens including p24, gp160, gp120, gp41 -Anti p24 is the first reliably detected antibody; declines as the viral tters rise in late infection -Envelope antibodies rise more slowly but stay high at end -ELSA for p24 useful early -Confirmation via second technique; Western blot utilized -HIV DNA PCR can be used for quantitative determination for viral load -Culture for HIV utilized for newborns whose mothers are HIV positive; assesses drug resistance -Confirmatory techniques are involved in confirmatory testing -Antigenic testing for newborns and screening NEGATIVE SENSE RNA VIRUSES: -Negative sense virus has on him an RNA dependent RNA polymerase -Negative sense positive -Hookup to ribosome to achieve protein synthesis -Three groups of viruses are important
IMMUNOLOGY AND IMPORTANT POINTS: -The innate immune system -Major barriers for entry include: -Lysosyme in nasal secretions -Intact skin -Glandular secretions -Natural flora -Mucous membranes -Professional phagocytic cells also part of the innate immune system - -Stages of phagocytic cell function: -production -mobilization -chemotaxis -Chemotactic factors -SERUM: c5a -MACROPHAGE: IL-8 -NEUTROPHILS: LTB4 -Opsonization: -Coating of particiles to improve digestion -Coating of antigen to assist with recogniztion -Coating with antibody -C3b is the opsonization factor -Macrophages have a complement receptor -The best phagocytosis is when the bacteria has antibody and complement -C3b binds to opsonized bscteria -Engulfment: -Formation of phagocytic vaculole -Lysosyme is not oxygen dependent -Oxygen dependent killing occurs with NADPH oxidase -CGD results when NADPH oxidase is missing -Metabolic events associated with phagocytosis: -Increased glycolysis via PPP -Increased lactic acid, decreased pH in phagosome -Increased oxygen consumption with production of toxic metabolites -Hypochlorite -Natural killer cells -Immune surveillance cells -Lymphoid cells are classified as large granular lymphocytes -NK cells found in spleen, lymph nodes, bone marrow, and peripheral blood -Lyse cells ncluding virus infected cells, antibody coated cells, tumor cells -Mechanism of killer cell lysis: -Both cytotoxic and NK cells have granules -Cell to cell binding, granule mobilization, and exocytosis involved in killing targed cells The adaptive immune system -Has memory -Must be induced. -Divided into recognition which is specific -Amplifiication due to cell division and activation of enzyme cascades -Regulation or control -Effector mechanisms MODES OF ACQUIISITION OF SPECIFIC IMMUNITY -Naturally acquired -Passive includes placental Ab transfer -Active involves recovery from disease -Artificially acquired -Passive: antitoxin administration (Rabies or tetanus abx) -Active: vaccination with MMR, DPT, DaPT Download 1.15 Mb. Share with your friends:
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