BIOL 4576 1st Edition Exam 4 Study Guide Lectures 12 16 Lecture 12 HIV AIDS associated neurologic disease opportunistic infections Normal CD4 T cell count 700 1000 cells per microliter of blood HIV count greater than 500 AIDS count less than 200 AIDS acquired immunodeficiency syndrome HIV human immunodeficiency virus The depression of immunity in AIDS allows for opportunistic infections to invade These may be infections that would not normally cause disease in a healthy person Opportunistic infections are the most common complication of HIV PML Progressive multifocal leukoencephalopathy is caused by JC virus JC virus antibodies are found in 70 of people and it usually acquired in childhood due to the fact that it is transmitted fecal orally It is a polyomavirus that has dsDNA and minichromosomes Symptoms fast behavioral and cognitive changes No headaches or fever Later cortical blindness problems in the occipital lobe not retina and paralysis Death in 1 year Pathology Focal demyelination lesions all over brain including brainstem and cerebellum CSF normal Oligodendrocytes have enlarged nuclei with inclusion bodies Changes in astrocyte morphology Pathogenesis JC virus enters brain either inside infected macrophages or infection of astrocytes which then spreads to oligodendrocytes Doesn t infect neurons A LOT of virus in the brain Diagnosis and treatment MRI shows white matter lesions in parieto occiptal lobe Viral DNA can be detected in some patients by PCR cART combo antiretroviral therapy extends survival for another year CMV Cytomegalovirus is a beta herpesvirus that is found in 80 of people but doesn t usually cause symptoms It is spread through the respiratory route It can also cause mono or a congenital disease called cytomegalic inclusion disease It goes latent in macrophages In AIDS it causes hepatitis colitis retinitis and neurologic diseases Neurologic disease it invades the brain through infected macrophages or it disseminates through the CSF It infects all types of brain cells including neurons ependymal cells and oligodendrocytes It can have 2 different pathologies once the brain is infected It can have a slow progressive panencephalopathy that causes death in 1 2 years It can also infect ependymal cells that cause ventricle enlargement and brain herniation which results in death with weeks to months HSV Both HSV1 and 2 cause diseases that are different from the diseases that they cause in immunologically normal people It causes 3 patterns of disease 1 acute necrotic hemorrhagic disease in the temporal lobes caused by HSV2 2 chronic subacute panencephalitis without the temporal lobe caused by HSV1 3 subclinical infection of brain parenchyma by HSV1 CMV and HSV can infect the same person at the same time Lecture 13 HIV AIDS associated neurologic disease HIV associated dementia Visna Retrovirus lentivirus enveloped conical capsid linear ssRNA RDDP RNA dependent RNA polymerase reverse transcriptase Characteristics 2 identical copies of genome per capsid RNA converted to DNA after entry but before uncoating a DNA copy called a provirus is integrated randomly into the host genome Pathogenesis it is spread horizontally via the respiratory route and vertically It infects macrophages and it carries the provirus It incubates for a long time 2 7 years The immune system fails to clear it but there is no immune suppression It enters the CNS through infected macrophages that then causes meningoencephalitis The virus replicates in many cells in the CNS but mostly microglial cells Pathology white matter of brain and spinal cord a lot of mononuclear infiltrates gliosis scar tissue of astrocytes microglial nodules large clumps of microglial monocyte cells areas of demyelination Onset of neurological symptoms is slow and without fever It can have progressive or intermittent paralysis that occurs over months CSF has pleocytosis and local antibody synthesis Maedi the respiratory disease that can be caused Visna virus There are lesions with mononuclear cells around them in the interstitial space of the lungs Visna and Maedi can affect the same sheep HIV Retrovirus lentivirus 3 protein groups gag structural proteins pol enzymes env envelope proteins regulatory genes Tat it increases transcription or DNA provirus its released from infected cells and can be up taken by other cells which will then kill them Nef it increases viral replication changes protein expression on cell surfaces decreases MHC1 expression and prevents apoptosis Macrophages and CD4 T cells are the target for HIV CD4 is the primary receptor and it binds to viral receptor gp120 There are also coreceptors that are found on these cells that are usually for chemokines These receptors bind to viral receptor gp41 The coreceptor on T cells is CXCR4 and the macrophage one is CCR5 The macrophage tropic strain is called R5 and the T cell one is called X4 HIV associated dementia HIV enters the brain at or before 2 weeks after infection HIV DNA and proteins can be recovered from the CNS at all points during infection after 2 weeks The symptoms usually associated with this are flu like as well as headache photophobia and nuchal rigidity The immune system usually keeps this in check but when AIDS hits that is no longer possible Symptoms abrupt onset over weeks to months 1 Forgetfulness and behavior changes 2 Loss of motor control 3 Global cognitive dysfunction spastic incontinent 4 Death within 3 6 years Neuropathology tissue wasting deepened sulci syncytia microglial nodules focal myelin loss Neuropathogenesis HIV entry into brain HIV enters the brain through infected macrophages and CD4 cells Viruses can also enter through direct infection of epithelial cells or astrocytes This infection can cause disturbances in the BBB Infection can cause release of TNFalpha which causes leakage Tat can upregulate cell adhesion molecules which allows more macrophages to enter the CNS Tat and gp41 production due to infection can cause the BBB to lose integrity Also the immune system secretes molecules which recruit more macrophages to the BBB HIV neurotropism when the virus enters the brain the R5 macrophage strain emerges Once there it infected many types of cells like oligodendrocytes but not neurons There are different cellular receptors in the brain GalC is most likely to be the primary receptor D6 which is another chemokine receptor is a coreceptor High levels of HIV RNA are correlated with dementia Within a host HIV can evolve differently