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HERPES — Complete Veterinary & Medical Guide

Note: Yeh topic veterinary aur human medicine dono mein important hai. Is guide mein dono perspectives cover kiye gaye hain — virology, pathogenesis, clinical signs, diagnosis, treatment, prevention, aur cases. Jo terms difficult hain unhe bracket mein explain kiya gaya hai.

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PART 1: CLASSIFICATION & TAXONOMY (Virus ka Khandaan)

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PART 2: STRUCTURE (Virus ki Banawat)

1. ENVELOPE (Outer lipid layer)
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2. TEGUMENT (Proteins ka layer — viral kinases hain iske andar)
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3. NUCLEOCAPSID (100 nm diameter, icosahedral shape, 162 capsomeres)
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4. CORE (Linear double-stranded DNA genome — 120-240 kb)

• Lipid envelope hone ki wajah se yeh virus ether aur detergents se destroy ho jaata hai
• Envelope glycoproteins (gB, gC, gD, gE/gI) attachment, entry, immune evasion ke kaam aate hain
• Yahi glycoproteins vaccine targets hain

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PART 3: REPLICATION CYCLE (Virus Kaise Copy Karta Hai)

• Virus pehle heparan sulfate proteoglycan se loosely attach hota hai (cell surface pe hota hai)
• Phir Nectin-1 receptor se tightly bind karta hai (yeh intercellular adhesion molecule hai, immunoglobulin family se)
• Aur HveA (Herpesvirus Entry Mediator A) se bhi — yeh TNF receptor family member hai, neurons pe express hota hai

• Envelope aur cell plasma membrane fuse ho jaate hain
• Capsid cytoplasm mein release hota hai
• Saath mein viral kinase aur cytotoxic proteins bhi release hoti hain

• Capsid nuclear pore ke paas jaata hai
• DNA genome nucleus mein inject hota hai

• Immediate Early (IE) genes — pehle express hote hain, DNA-binding proteins banate hain
• Early (E) genes — DNA polymerase, thymidine kinase banate hain
• Late (L) genes — structural proteins (capsid, envelope glycoproteins)

• Pehle circular concateneric forms bante hain
• Phir rolling circle mechanism se linear DNA banata hai (toilet paper roll ki tarah!)

• Core + capsid nucleus mein assemble hota hai
• Envelopment nuclear membrane se hota hai
• Endoplasmic reticulum aur Golgi se transport — glycosylation Golgi mein hoti hai

• Mature virions vesicles mein cell surface par aate hain
• Release ke saath cell death hoti hai

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PART 4: PATHOGENESIS — LATENCY & REACTIVATION (Sabse Important Concept!)

1. Virus mucosal surface ya skin pe inoculate hota hai
2. Epithelial cells mein replicate karta hai (incubation 4–6 days)
3. Cell lysis se vesicles banate hain erythematous base ke saath
4. Virus sensory nerve endings mein ghusta hai
5. Retrograde transport (periphery se nucleus ki taraf) sensory neuron ke axon mein
6. Dorsal Root Ganglia (DRG) mein pahunhcta hai — yahan latent ho jaata hai

• Virus ki DNA extrachromosomal ya integrated form mein neuron nucleus mein rehti hai
• Sirf LAT (Latency-Associated Transcripts) express hote hain — yeh micro-RNAs banate hain jo immediate early genes ko suppress karte hain
• Virus "so raha hota hai" — immune system pakad nahi sakta

• Koi trigger aata hai → LAT expression kamm hoti hai → IE genes on hote hain → virus replicate karta hai
• Anterograde transport (nucleus se periphery ki taraf) peripheral nerve ke zariye
• Skin/mucosa mein vapas aake vesicles banata hai

• Stress (physical ya psychological)
• Fever / systemic illness
• UV light (sunlight)
• Immunosuppression
• Menstruation (progesterone effect on immunity)
• Surgical/dental trauma
• Malnutrition, parasitic burden

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PART 5: IMPORTANT ANIMAL HERPESVIRUSES

5A. Equine Herpesvirus (EHV) — Ghore

• EHV-1: Abortion, neonatal foal disease, rhinopneumonitis (naak ki soojan), myeloencephalopathy (brain/spinal cord disease)
• EHV-4: Predominantly respiratory disease (rhinopneumonitis)
• EHV-3: Coital exanthema (genitalia pe lesions)

• Naak se discharge, khansee, bukhar
• Lymphadenopathy (lymph nodes ki sujaish)
• Pregnant mares mein: Abortion (usually last trimester, bina kisi warning ke) — "abortion storm" — ek herd mein multiple abortions
• Neurological form (EHV-1 Myeloencephalopathy): Hindlimb ataxia (larkhat), urinary incontinence, recumbency

• Intranuclear inclusion bodies (Cowdry Type A)
• Endothelial vasculitis → ischemia

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5B. Feline Herpesvirus (FHV-1) — Billi

• Severe sneezing, nasal discharge (pehle serous, phir mucopurulent)
• Conjunctivitis (ankhein red, discharge)
• Keratitis — corneal ulcers → dendritic ulcers → possible blindness
• Bukhar, anorexia, depression
• Neonatal kittens mein: Severe systemic disease, encephalitis, death

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5C. Canine Herpesvirus (CHV-1) — Kutta

• Sudden onset, rapid progression
• Crying, weakness, nasal discharge
• Abdominal pain, yellowish-green feces
• Scattered hemorrhagic petechiae on body
• Death within 24–48 hours

• CHV-1 optimal replication temperature: 35–36°C (normal puppy body temp is < 37°C)
• Puppy thermoregulation karna nahi jaanta → body temp low → virus multiply karta raha
• Immunity nahi hoti neonatal period mein

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5D. Bovine Herpesvirus 1 (BHV-1) — Gaye/Bail

• IBR (Infectious Bovine Rhinotracheitis): Nasal/respiratory disease, bukhar, red nose (yahi "Red Nose Disease" kehte hain)
• IPV (Infectious Pustular Vulvovaginitis): Female genitalia pe pustules
• IPB (Infectious Pustular Balanoposthitis): Male genitalia pe pustules
• Neonatal systemic disease: Encephalitis, death

• High fever (40–42°C)
• Serous → mucopurulent nasal discharge
• Nasal mucosa bright red → "fire nose"
• Conjunctivitis, lacrimation
• Dyspnea, coughing
• Doodh production mein giraaawat
• Pregnant cows: abortion (usually 4–8 months gestation)

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5E. Pseudorabies Virus (PRV) / Aujeszky's Disease — Sooar (Pig)

• Pigs (Adults): Respiratory disease, mild
• Pigs (Piglets): CNS signs — tremors, convulsions, death
• Cattle/sheep/dogs (dead-end hosts): Intense pruritus (khujli) — "Mad Itch" → animal khud ko damage kar leta hai, death

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5F. Marek's Disease Virus (MDV) — Murgi (Poultry)

• Classic form: Peripheral nerve paralysis — "Splits" posture (ek pair age, ek peeche) — sciatic nerve
• Acute form: Sudden deaths, lymphoma in visceral organs
• Tumor formation in organs (liver, spleen, gonads)
• Iris ka grey ya white hona (greyeye)

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PART 6: GENERAL PATHOLOGY (Histopathology)

• Vesicles on erythematous base — "dew drop on a rose petal"
• Vesicle → Pustule → Ulcer → Crust → Healing (scar uncommon)
• Mucosal erosions, nasal discharge, conjunctivitis

• Ballooning degeneration of infected cells — cells phool jaate hain
• Multinucleated Giant Cells (Syncytia) — multiple cells fuse ho jaate hain — yeh herpes ki HALLMARK hai
• Cowdry Type A Intranuclear Inclusion Bodies — nucleus ke andar basophilic ya eosinophilic inclusions — viral assembly sites hain
• Intense inflammatory infiltrate (mononuclear cells)
• Vascular changes: perivascular cuffing, hemorrhagic necrosis (especially CNS mein)

• Lesion ki base se scraping lao
• Multinucleated giant cells aur Cowdry Type A inclusions dikhte hain
• Simple, quick — no special equipment needed

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PART 7: LABORATORY DIAGNOSIS

• Scraping se multinucleated giant cells dekho
• Fast, cheap — but not type-specific

• Vesicle fluid, nasal swab, CSF lao → cell culture (HeLa cells, human embryonic fibroblasts) mein inoculate karo
• HSV 1–3 days mein cytopathic effect (CPE) deta hai — cells round, enlarged ho jaate hain
• Syncytia bhi ban sakti hain
• Specimens cold (4°C) rakhna — freeze mat karo

• Gold standard aaj kal
• Vesicle fluid, CSF, nasal swab se viral DNA detect karo
• HSV-1 vs HSV-2 distinguish kar sakta hai
• Sensitivity bahut high hai

• Tissue ya smear pe antibodies lagate hain fluorescent label ke saath
• Specific viral antigen detect karta hai

• Primary infection ke diagnosis ke liye useful (rising antibody titers)
• Recurrent disease mein NOT useful — antibodies already hain, significant rise nahi aati
• Type-specific ELISA available hai

• β-galactosidase expressing cell line use hoti hai
• HSV infection pe enzyme produce hoti hai → colored substrate se detect hoti hai
• Modern virology labs mein use hota hai

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PART 8: TREATMENT PROTOCOL (Complete & Accurate)

Mechanism of Antiviral Drugs

Step 1: Virus thymidine kinase → Acyclovir ko MONOPHOSPHATE banata hai
         (sirf infected cells mein yeh step hota hai — selectivity yahan se aati hai)
Step 2: Host cell kinases → Diphosphate → Triphosphate
Step 3: Acyclovir Triphosphate → Viral DNA polymerase ko compete karta hai
Step 4: DNA mein incorporate ho jaata hai → Chain TERMINATE ho jaati hai
         (kyunki acyclovir mein 3'-OH group nahi hota — extension nahi ho sakti)

• Thymidine kinase mutation → drug activate nahi ho sakta
• DNA polymerase mutation
• Mainly immunocompromised patients mein milta hai

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Treatment Protocols (Human — Reference ke liye)

• Acyclovir 200 mg 5x/day OR 400 mg TID × 7–10 days
• Valacyclovir 1000 mg BD × 7–10 days
• Famciclovir 250 mg TID × 7–10 days

• Acyclovir 400 mg BD (chronic)
• Valacyclovir 500 mg OD

• Acyclovir 5 mg/kg TID (IV) × 7 days

• Acyclovir 10 mg/kg TID (IV) × 14–21 days

• Acyclovir 15 mg/kg 5x/day (oral suspension) × 7 days (peds)
• Valacyclovir 1g BD × 7 days (adults)

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Veterinary Treatment Protocols

• No specific antiviral for cattle in routine practice
• Supportive treatment:
  • NSAIDs (Flunixin meglumine 2.2 mg/kg IV BD, Meloxicam 0.5 mg/kg IV/IM)
  • Antibiotics for secondary bacterial pneumonia (Enrofloxacin, Oxytetracycline, Penicillin + Streptomycin)
  • Intranasal oxygen if severe dyspnea
  • IV fluids, vitamins (A, C, E)
  • Isolation of affected animals

• Warming puppies (incubator 29–32°C) — temperature raise karne se viral replication ruk jaati hai
• Hyperimmune serum (agar available ho)
• Supportive fluids (glucose solution SQ)
• Antiviral: Acyclovir cautiously (nephrotoxic in pups)
• Prognosis: Poor if symptomatic neonates

• Dead-end hosts (cattle, dogs) — invariably fatal
• Affected animals euthanize karo
• No specific antiviral approved

• No treatment — Prevention only (vaccine)

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PART 9: PAKISTAN MEIN AVAILABLE BRANDS

Antiviral Drugs

• IBR Vaccine: Bovilis IBR (MSD Animal Health) — intranasal ya injectable
• EHV Vaccine: Duvaxyn EHV 1,4 — horses ke liye
• FHV Vaccine: Felocell CVR-C (Zoetis), Nobivac Tricat — cats ke liye
• Marek's Vaccine: Rispens + HVT bivalent vaccine — chicks ke liye (hatchery level)
• PRV (Aujeszky's) Vaccine: Suis Porvac — pigs ke liye

Supportive Drugs (Vet Practice)

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PART 10: PREVENTION & CONTROL

• IBR (BHV-1): Killed or modified live vaccine — herd vaccination zaroori
• EHV-1/4: Killed vaccine every 6 months — especially pregnant mares
• FHV-1: Core vaccine for all cats — killed or MLV
• CHV-1: Eurican Herpes vaccine (Europe mein available) — bred bitches ko
• Marek's: Day-old chicks ko hatchery mein — HVT + Rispens bivalent

• New animals quarantine (minimum 2–3 weeks)
• Separate stressed/sick animals
• Disinfectants effective (bleach 1:32, Virkon, Glutaraldehyde — lipid envelope destroy karte hain)
• Separate nasal/vaginal discharge contaminated equipment
• Heat aur drying bhi virus kill karta hai
• Gloves pehno — herpetic whitlow (finger mein lesion) humans ko bhi ho sakta hai

• Overcrowding avoid karo
• Adequate nutrition, vitamins
• Minimize transport stress
• Proper ventilation

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PART 11: CONCEPT SUMMARY TABLE — Kaunsa Virus, Kaunsa Animal, Kya Disease?

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PART 12: REVIEW QUESTIONS

Ans: Linear, double-stranded DNA (dsDNA), 120–240 kb

Ans: Sensory neurons (dorsal root ganglia mein) — kyunki neurons divided nahi hote (non-dividing cells) aur immune surveillance low hai; LAT transcripts immediate early genes ko suppress rakhte hain

Ans: Viral thymidine kinase specifically infected cells mein acyclovir ko monophosphate mein convert karta hai; host kinases further activate karte hain; Acyclovir triphosphate viral DNA polymerase ko compete karke chain termination karta hai. Uninfected cells mein viral TK nahi hota → drug activate nahi hota.

Ans: Cats mein acyclovir ki bioavailability poor hai aur nephrotoxicity ka risk high hai; Famciclovir preferred hai.

Ans: CHV-1 optimal replication 35–36°C pe hoti hai; puppies ko warm rakhne se body temperature 38°C se upar jati hai, jo viral replication inhibit karta hai.

Ans: Multinucleated giant cells (syncytia) aur Cowdry Type A intranuclear inclusion bodies

Ans: EHV-1 infected herd mein multiple pregnant mares mein simultaneously ya rapidly abortion — usually last trimester mein — bina prior warning ke; endothelial vasculitis se placental ischemia aur fetal death

Ans: Cattle dead-end host hain — PRV CNS infection severe pruritus produce karta hai; animal compulsively scratch karta hai skin tear ho jaane tak; invariably fatal; no treatment

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PART 13: CLINICAL CASES

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CASE 1: Equine Herpesvirus — Abortion + Neurological Form

• Fever 40.5°C
• Hindlimb weakness, ataxia (larkhat)
• Bladder distension (urine retain kar rahi hai)
• Nasal discharge — serous
• Aborted fetuses: autolyzed, no obvious external lesions

• Multiple abortions → herd level disease → infectious etiology
• Neurological signs + abortion combination → EHV-1 Myeloencephalopathy (EHM)
• EHV-4 usually sirf respiratory karta hai, abortion rare
• DDx: Leptospirosis (abortion), Rhinopneumonitis (respiratory), Viral Arteritis

• Nasopharyngeal swab → PCR for EHV-1 → Positive
• Aborted fetus: placenta, fetal tissues → PCR positive, intranuclear inclusions on histopath
• Paired serology (acute + convalescent) → rising titers

• Affected mare: Valacyclovir 40 mg/kg QID oral
• Flunixin meglumine 1.1 mg/kg IV BD
• DMSO 1 g/kg (10%) IV slow drip — spinal cord edema ke liye
• Bladder catheterize karo (urinary retention)
• Corticosteroids (dexamethasone) — controversy hai but kuch vets use karte hain acute EHM mein
• IV fluids, nutritional support

• Affected horses ISOLATE karo — minimum 3 weeks
• Aborted mares ko separate stall
• All horses temperature monitor karo twice daily
• New horses quarantine
• Emergency vaccination consider karo (EHV-1,4 killed vaccine)
• Disinfect paddocks, equipment

• EHV-1 ek hi virus se 3 syndromes: respiratory, abortion, neurological
• Abortion storm + neurological signs = EHV-1 until proven otherwise
• Valacyclovir horses mein better bioavailability > acyclovir
• Latency trigeminal ganglion mein — stress se reactivate

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CASE 2: Feline Herpesvirus — Shelter Cat with Eye Disease

• Bilateral conjunctivitis (severe) — ankhein puri tarah bandh — purulent discharge
• Nasal discharge — mucopurulent
• Sneezing frequent
• Temp 39.9°C
• Cornea — left eye mein dendritic ulcer visible under slit lamp (fluorescein stain se green glow)
• Body condition: poor, thin
• Lymphadenopathy — submandibular nodes enlarged

• Shelter environment → stress → primary FHV-1 infection OR reactivation
• Respiratory signs + conjunctivitis + keratitis = FHV-1 (Feline Viral Rhinotracheitis)
• DDx: Calicivirus (oral ulcers prominent), Chlamydophila felis (conjunctivitis only, no corneal), Bordetella
• Dendritic corneal ulcer → highly specific for FHV-1

• Conjunctival swab → PCR for FHV-1 → Positive
• Fluorescein corneal stain → dendritic branching ulcer → confirms herpetic keratitis

• Famciclovir 90 mg/kg PO BD × 3 weeks (safe in cats — do NOT use acyclovir)
• Doxycycline 5 mg/kg PO OD × 3 weeks (secondary bacterial + rules out Chlamydophila)
• Lysine 250 mg PO BD (arginine antagonist — some benefit)

• Cidofovir 0.5% eye drops — BD (better than trifluridine, less frequent dosing)
• Artificial tears q4h — keep cornea lubricated
• E-collar (Elizabethan collar) — rubbing prevent karo
• DO NOT use corticosteroid eye drops — yeh herpes mein contraindicated hain — corneal perforation ho sakti hai

• Nutritional support — high-protein wet food
• Steam inhalation (nasal congestion ke liye)
• Warm place rakhna

• Vaccination schedule follow karo (FHV-1 core vaccine)
• Stress minimize karo
• On reactivation: famciclovir course repeat

• Acyclovir cats mein nephrotoxic → Famciclovir use karo
• Dendritic ulcer = FHV-1 hallmark
• Corticosteroid eye drops contraindicated herpes keratitis mein
• Shelter stress → latent virus reactivation → disease
• Kitten unvaccinated tha → vaccination zaroori

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• Medical Microbiology 9e (Murray) — HSV structure, replication, pathogenesis, diagnosis
• Goldman-Cecil Medicine — HSV pathobiology, clinical manifestations, treatment
• Andrews' Diseases of Skin — Genital herpes, orolabial herpes, treatment protocols
• Lippincott Pharmacology — Acyclovir mechanism of action
• Jawetz Medical Microbiology — Herpesviridae family overview

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