Exam II: Virology III Flashcards
Retroviridae
Diploid, positive ssRNA, associated reverse transcriptase
- Lentivirus group: human immunodeficiency virus (HIV)
- Oncovirus group: human T Cell Leukemia (HTLV) and adult T cell leukemia
A typical, “minimal” retrovirus consists of:
an outer envelope which was derived from the plasma membrane of its host, many copies of an envelope protein embedded in the lipid bilayer of its envelope, and a capsid, which is a protein shell containing two molecules of RNA “diploid” and reverse transcriptase
Structure and Genes of HIV
+RNA diploid and non segmented
Lentivirus in the retrovirus family
HIV virion contains enveloped truncated conical capsid (type D),2 copies of positive ssRNA, reverse transcriptase (RNA dependent DNA polymerase), integrase, and protease
GP120 and GP41 (41K MW) and they are important in attachment and vaccine development attempts
Integrase involved once the RNA is transcribed into DNA the DNA must integrate into DNA of the host
Proteases are encoded in RNA and process proteins that will make the capsid of the virus so it can be packaged and released
HIV Transmission
Blood and blood products: needle drug injection
Sexual intercourse: semen and vaginal secretions
Vertical infection: mother to infant
Latency promotes the spread because either undetected or patients relax on protecting others/themselves
STDs also promote the spread by helping the virus gain access to epithelial tissue
No transmission by casual contact
HIV Replication
Starts with attachment to the cell by binding to the CD4 receptor, then fusion between virus and cell membrane
Enters with its capsid, RNA, and RT, then uncoating of the capsid (removal) so that the RNA can be copied/transcribed via RT into DNA
ssRNA to ssDNA = complementary DNA to genome, which can be introduced into the nucleus and integrated via integrase into the host
Then pack of pro-virus inside the cell and replication will continue with replication machinery of the cell since we have DNA and not RNA anymore, then transcribed
Once RNA is produced, it will leave the nucleus and part of the RNA will act as mRNA which will produce proteins of the virus including RT and capsid proteins
All of these will be made by the use of translation machinery= ribosomes and ER
Virus needs a specific protease to process the proteins to cut down large proteins = essential for the synthesis of the virus and then these proteins will join the genomic RNA (similar to virus RNA), and this will be packaged in the capsid and goes through the membrane via budding and this will cause the release of the virus = no lysis in this case
Pathogenesis of HIV/AIDS
- The stages of HIV disease correlate with a progressive spread of HIV from the initial site of infection to lymphoid tissues throughout the body; infect CD4 T cells and dendritic cells
- The immune response of the host temporarily controls acute infection but does not prevent establishment of chronic infection of cells in lymphoid tissues; viremia occurs because virus will be released in the blood after replication
- The host’s immune response temporarily controls acute infection; this diminishes the number of viruses within the blood = latency period
- But establishment of chronic infection of cells in lymphoid tissues succeeds
- Cytokines produced in response to HIV and other microbes serve to enhance HIV production and progression to AIDS
- Infection occurs with another virus or bacterium leading to the activation of the infected CD4 cells causing second viremia that invades every organ and the fight against the disease becomes impossible leading to AIDS
Clinical Course of HIV
Blood-borne HIV virus (plasma viremia) is detected early after infection. Tests detect DNA after 6 days
It may be accompanied by systemic symptoms typical of acute HIV syndrome
The virus spreads to lymphoid organs, but plasma viremia falls to very low levels (only detectable by sensitive reverse transcriptase polymerase chain reaction (rtPCR) assays) & stays this way for many years
CD4+ T cell counts steadily decline during this clinical latency period, because of active viral replication and T cell destruction in lymphoid tissues
As the level of CD4+ T cells falls, there is increasing risk of infection and other clinical components of AIDS
Clinical Syndromes Associated with HIV
“AIDS”: opportunistic infections, cancers, CNS dysfunction
The initial symptoms: mono/flu and “aseptic” meningitis or rash occurring up to 3 months after infection
Full blown AIDS occurs when CD4 T cells are <200/ul
Opportunistic Infections
Viral infections: herpesvirus infections (HSV, VZV, EBV, CMV) when T cells under 50 cells/ul, and papovavirus infections
Bacterial infections: T and other mycobacteria whenT cells between under 400/ul, and various bacteria, including members of normal flora
Fungal infections: Pneumocystis jirovecii (carinii) pneumonia when T cells under 200/ul, oral candidiasis with Candida albicans (thrush) when T cells between 250-500/ul, and Cryptococcus neoformans- Cryptococcal meningitis (T cells < 200/ul)
Protozoan infections: Toxoplasma gondii- Toxoplasmosis
HIV Anti-Viral Therapy
- Attachment/entering: Fusion inhibitors
- Reverse transcription: Viral RNA to DNA via reverse transcriptase inhibitor
- Integration & Transcription: viral DNA joins host DNA making multiple viral RNAs via integrase inhibitors
- Translation- producing viral proteins
- Viral protease: cleaving viral proteins via protease inhibitors
- Assembly & budding: getting out; no drug development because it is already too late
RT, Protease Inhibitors, and HAART
- Reverse transcriptase inhibitors:
nucleoside analogs= AZT (Zidovudine), and others (ddI, 3TC (Lamivudine), d4T, ddC)
Non-nucleoside analogs: Delavirdine and Nevirapine - Protease inhibitors: Indinavir, Nelfinavir, and Ritonavir
- HAART (highly active anti-retroviral therapy): combination of drugs because it is unlikely that the virus will be resistant to all three in the combination
Togaviridae
Alpha virus group: Western Equine encephalitis virus, Eastern Equine encephalitis virus , Venezuelan Equine encephalitis virus
Mosquito borne diseases where wild birds are reservoirs
Viremia, arthralgia, and mild fever
CNS infection/Encephalitis: highly linked with horses
fatality rates of 30-70%
Present worldwide, especially in the spring ideal conditions for viral replication and vector populations are large
Vaccines have been developed against the encephalitic diseases
Togaviridae: Rubella
Transmission via respiratory droplets
Crosses placenta and is teratogenic, which causes abnormal prenatal development and serious consequences during first trimester of gestation
Congenital Rubella Syndrome: group of physical abnormalities that have developed in an infant as a result of maternal infection and subsequent fetal infection with rubella virus. It is characterized by rash at birth, low birth weight, small head size, heart abnormalities, visual problems and bulging fontanel
Attenuated vaccine: single strain, part of MMR
Negative Sense RNA Viruses
All of these viruses: are enveloped, virion associated enzymes, and replicate in the cytoplasm, but orthomyxovirus replicate in the nucleus
Linear non-segmented ssRNA:
Paramyxovirus (Mumps, Measles, RSV, Parainfluenza)
Rhabdovirus (Rabies & VSV)
Filovirus (Ebola & Marburg)
Linear ssRNA with 8 segments
Orthomyxovirus (Influenza)
Linear Circular ssRNA with 3 ambisense segments
Bunyavirus (California encephalitis, Hantavirus & La Cross)
Circular ssRNA with 2 segments: 1 negative sense & 1 ambisense [Ambisense RNA viruses resemble negative-sense RNA viruses, except they also translate genes from the positive strand] = Arenavirus (Lassa fever & LCMV)
Negative Sense RNA Virus Life Cycle
Replicated in cytoplasm but some must go in the nucleus
Virus is phagocytosed by the cell and then the ultimately the RNA will be released after uncoating and then it can be replicated
Copy of the viral RNA (vRNA) is the cRN(complementary)
Viral RNA can be made into two types: cRNA used as a template to make the vRNA that will be packaged and produced, and the other will be made mRNA that will produce the proteins and enzymes that are needed for translation = need these for replication to become successful
Paramyxoviridae: Parainfluenza and RSV
ssRNA, enveloped, helical nucleocapsid
- Parainfluenza: single helical nucleocapsid glycoprotein
Croup =laryngotracheobronchitis, common cold, and bronchitis - Respiratory syncytial virus (RSV): negative ssRNA and major cause of bronchiolitis and pneumonia in infants
