1. Selected Viral Pathogens

Transcription

1 Chapters 19-24: Selected Pathogens 1. Selected Viral Pathogens 2. Selected Bacterial Pathogens 1. Selected Viral Pathogens Influenza (flu) (pp ) Caused by various strains of Influenzavirus (RNA, enveloped): H spike (hemagglutinin) mediates attachment 15 known types, determines host range N spike (neuraminidase) aids in detachment from host during release 9 known types H & N combinations distinguish different strains (e.g. H1N1) 8 RNA fragments encoding only 10 polypeptides 1

2 Influenzavirus A: Influenzavirus Genera natural hosts include aquatic birds, pigs new strains can occasionally jump from animal hosts to humans source of most dangerous outbreaks in humans Influenzavirus B: limited almost exclusively to humans not as dangerous Influenzavirus C: generally limited to humans, less common Generation of New Strains Antigen Drift: changes in viral genome due to natural mutation viral RNA-synthesizing enzymes are relatively error-prone, lack proofreading capability of most DNA polymerases change is gradual, not usual source of pandemics Antigen Shift: new variants due to simultaneous infection of same cell with different strains (usu. in bird or pig) can produce new H:N combos via shuffling of RNA frags. limited primarily to type A, source of most pandemics Antigenic Drift 3 Influenzavirus 1 differs slightly from virus 1. 1 Influenzavirus 1 enters host cell. Antigenic Shift 3 Influenzavirus 3 very different from 1 Influenzaviruses 1 and 2 viruses 1 and 2. enter host cell. Virus 1 Virus 2 2 Mutations in 2 Genes and antigen genes antigens from occur during both viral types replication are incorporated within host cell. into new virions. Number of cases Number of cases Time (years) Biennial outbreaks of mild influenza Time (years) Occasional outbreaks of very severe influenza 2

3 Family Herpesviridae Enveloped, ds DNA viruses, several of which are common pathogens: Human Herpes Virus-1 & 2 (HHV-1 & HHV2) aka Herpes Simplex Viruses responsible for fever blisters, genital herpes Human Herpes Virus-3 (HHV-3) aka Herpesvirus Varicella Zoster responsible for chicken pox, shingles Human Herpes Virus-4 (HHV-4) aka Epstein-Barr virus (EBV) Herpes Simplex (pp ) Caused by HHV-1 and HHV-2: HHV-1 very common & typically benign infection found in ~90 % of the U.S. population responsible for cold sores & fever blisters transmission through respiratory or oral routes HHV-2 responsible for genital herpes from sexual contact Outbreak of facial/oral lesions due to HHV-1: due to latent infection (provirus) of trigeminal ganglion nerves lesions triggered typically by stress or UV exposure 3

4 Genital Herpes The STD genital herpes is primarily caused by Human Herpesvirus 2 (HHV-2): oral-genital transmission of HHV-1 can also cause genital lesions transmission due to sexual contact is followed by a ~1 wk incubation period and then: burning sensation followed by the appearance of painful blister-like vesicles that eventually heal like all herpes viruses, HHV-2 infection results in latent provirus, periodic reactivation antiviral drugs can manage, but not cure the disease Chicken Pox & Shingles (pp ) Chicken pox is caused by Herpesvirus varicellazoster (HHV-3): due to symptoms of initial infection respiratory portal of entry skin cells then infected to cause pox becomes latent infection in spinal cord Shingles is due to the activation of latent HHV-3: only occurs in people who have had chicken pox appears in people who are immunologically weakened due to stress or age 4

5 Epstein-Barr Virus (pp ) The Epstein-Barr virus (EBV) or human herpesvirus 4 (HHV-4) is responsible for: MONONUCLEOSIS transmitted via saliva virus infects B cells sore throat, swollen lymph nodes, extreme fatigue Burkitt s & other LYMPHOMAS malignant lymphocyte cancers chromosomal translocations Human Immunodeficiency Virus (HIV) & AIDS (pp ) A type of Lentivirus (in the family Retroviridae) genetic material is RNA contains reverse transcriptase which copies viral RNA into DNA infects human T H cells, macrophages dendritic cells & smooth muscle cells HIV Transmission Infection occurs via body fluids of an infected individual: blood contains the greatest density of HIV virions semen also contains significant numbers other fluids (e.g., saliva) generally don t contain a sufficient density of HIV virions to transmit infection Transmission typically occurs through: sexual contact blood transfusions puncture with contaminated needles 5

6 Attachment & Penetration gp120 spikes bind viral receptor on target cells CD4 in association with CXCR4 (T H cells) OR CD4 in association with CCR5 entry via fusion Synthesis vs Latency DNA is inserted into host cell chromosome (provirus) can remain latent for years, or express viral genes virions can be latent too! From HIV infection to AIDS 6

7 2. Selected Bacterial Pathogens Genus Staphylococcus Staphylococcus aureus (pp , ): various strains cause types of skin infections, pneumonia, food poisoning, toxic shock syndrome depending on extra genes acquired by transformation, transduction features that contribute to its virulence: protein A binds F C of IgG, prevents opsonization produces coagulase, hyaluronidase, staphylokinase β-lactamase (penicillinase) Staphylococcal Food Poisoning The most common cause of gastroenteritis is that caused by the exotoxin enterotoxin produced by certain strains of Staphylococcus aureus: enterotoxin gene acquired by phage transduction superantigen triggering massive immune response in gut resulting in vomiting & severe diarrhea suspect foods are meats that have been cooked and then not handled or stored properly cooking kills all microbes initially subsequent S. aureus contamination due to handling, poor storage conditions can lead to illness 7

8 Typical case of Food Poisoning S. aureus introduced to cooked food by handler extended storage at room temperature allows bacteria to proliferate & release enterotoxin ingested enterotoxin from food causes symptoms of food poisoning Methicillin-resistant S. aureus (MRSA) Methicillin is a β-lactam antibiotic that most strains of S. aureus are sensitive to. penicillinase resistant, rarely used clinically MRSA infections usually treated with vancomycin a glycopeptide that is not absorbed through oral ingestion, must be intravenous vancomycin resistant strains (VRSA) exist and must be treated with other antiobiotics Typically a nosocomially acquired infection transmission via health care workers, fomites Streptococcus pyogenes (pp ) cause of scarlet fever, pharyngitis, rheumatic fever have capsule made of hyaluronic acid part of extracellular matrix, discourages IR produce protein M which interferes w/complement also produce streptokinase, C5a peptidase secrete erythrogenic toxins (cause fever, rash) 8

9 2 1 Streptococcus pyogenes in respiratory droplets from a nearby cough or sneeze enter the body Pharyngitis results; the back of the pharynx reddens, lymph nodes swell, and tonsils abscess. Fever, malaise, and headache are typical. 3 If bacteria spread to trachea, laryngitis may result. 4 Infection of the bronchi may cause bronchitis Erythrogenic toxins trigger scarlet fever, a rash that spreads from the chest, a strawberry-red tongue, headache, chills, and muscle ache. 6 Rheumatic fever may develop with pain in heart and joints. Mycobacterium tuberculosis cause of tuberculosis (kills ~2 million people/yr) typically transmitted via inhalation of droplets battle between host and pathogen takes place in the alveoli phagocytosis by alveolar macrophages in susceptible individuals, some bacilli can survive and proliferate within macrophages inflammatory signals recruit more phagocytes to area resulting in formation of a tubercule, a walled off structure enclosing the infected cells tubercules can ultimately rupture leading to spread of the pathogen throughout the body: referred to as miliary TB such systemic infection can lead to the gradual consumption of infected tissues, hence TB s more traditional name anti-mycobacterial drugs can be effective (rifampicin, isoniazid) though resistance is a problem 9

10 1 Inhaled respiratory droplets Bronchiole Respiratory bronchiole Macrophage Alveoli Alveolus Incipient tubercle Mycobacterium 2 Blood vessel 3 Collagen fibers Mycobacterium Caseous necrosis Tubercle Ruptured tubercle Bronchiole Alveolus 4 5 Blood vessel Primary tuberculosis infection Secondary or reactivated tuberculosis Key Terms hemagglutanin neuraminidase antigenic drift antigenic shift tubercule 10