. After ex pos ure to a varian t of Citro bacter [reundii , suckling and adult mice developed transmissible murine coloni c hyper plasia of the same degree of seve rity . Muco sal hyperpl asia was most severe 2 to 3 weeks after inocu lation and then regressed . Suckling mice had a high morta lity because of seconda ry infla mmat ory and erosive changes . Severe hyper plasia was char acterized by mitotic activity along the ent ire crypt column and surface mucosa .Tra nsmissible m uri ne colo nic hyperplasia is a nat ura lly o ccu rr ing infectious di se ase of mi ce , cha ra cte rize d b y mu co sal hyp e rpl asia of th e d ista l col on . Erosio n a nd inf la m ma tio n ma y ac co m pa ny t he hyp e rpl asia. It is ca use d by a varia nt of Citrobacter [reundii [ I I. In a na tural o u tb re a k ret arded g ro wth , ruffle d fur , soft feces , o ccasio na l rect al pr ol a pse a nd mod erat e mort ality were see n in mic e a t th e lat e s uc kling a nd ea rly we an ling ag es. T he se signs we re se e n rarel y in a d u lts [3].T he ac tua l incid ence of tr an smi ssibl e mu rin e col on ic hyp erpl a sia in mouse co lo nies is difficult to d e termin e , since th e ine xp erien ced o bserve r ma y not not e the vag ue cl in ical signs a nd fre q uent lac k o f o bv io us gross le sion s . A num b e r o f po ssibl y rel at ed synd ro mes of mic e ha ve be en de scri be d b y o t he r la bo ra tories .T wo o f th ese la b orat orie s isol at e d varia nt s of C. fre undii a nd rep ro duce d co lo nic hyp e rpl a sia in experi me nt a lly in o cul a te d mic e [2 , 5 , 6 ]. T he pat ho lo gy de scribe d in th e se re po rts parti all y re sembl ed th at for tr an smissibl e murin e colonic hyp e rpl asia , b ut th ere a re diffe re nc es th at m ak e it di fficult to sta te t he y a re a ll th e sa me di se a se p roce ss . T hese d iffe re nces ma y be re al o r ma y b e ca use d b y vari at io n in co nd it io ns a nd tim e o f sa m p ling . T he ag es of mi ce a nd histo gen e sis o f th e lesion s were not given in re po rt s of ei t her the natu ral o r exp e rime n ta l di se ase . Ot he r possibl y rel at ed le sion s , of un d et e rmin ed ca us e , have bee n d escribe d [3 , 11] . T hese we re cl assi fied as co litis cystica [3 ] a nd ne opl asia [11] a n d had down growth of mu co sal e pi the lium into t he s u b m ucosa . E p ithe lia l d o wn gro wth ha s not bee n see n in tran smi ssible murin e col onic hyp erplasia o r o t he r hyp erpla st ic di se a se s kn o wn to be associa te d wit h C. freu ndii.Ou r stu dy exa mi ne s the path o gen e sis o f t his di se ase in N I H Sw iss m ice a nd co m pa res le sion s to th o se found by oth ers . Becau se of report ed clinical di fferences 223

C 57 BL/6 mice developed resistance to lethal intravenous challenge with virulent (Moscow strain) ectromelia virus between 2 and 3 weeks of age. The fraction of C57 BL/6 mice in which virus was detected in spleen was significantly lower than for DBA/2 mice by day 3. Thereafter, C 57 BL/6 mice had significantly reduced virus titers in spleen compared with those of DBA/2 mice. Resistance was abrogated by treatment with anti-asialo GM1 gammaglobulin, which blocks NK cell activity, or with anti-interferon (IFN) alpha, beta. C 57 BL/6 mice carrying the bg/bg mutation, associated with a deficiency of NK cells, were highly susceptible to lethal infection as were athymic mice derived from a resistant genetic background. Virus titers in spleens of C 57 BL/6 mice treated with anti-asialo GM1 or anti-IFN alpha, beta were significantly higher 4 days after virus challenge than were titers in C 57 BL/6 mice treated with normal rabbit serum. The results strongly suggest that genetic resistance to lethal ectromelia virus infection requires non-specific host defenses such as NK cells and IFN alpha, beta that are activated during the first 3 to 4 days of infection.

No abstract

The pathogenesis of rat virus (RV) infection was studied in random-bred Sprague-Dawley rats after oronasal inoculation of a recent RV isolate designated RV-Yale (RV-Y). RV-Y was pathogenic for rats inoculated as infants (2 days) whereas rats inoculated as juveniles (4 weeks) had asymptomatic infection and no lesions. Rats inoculated as infants developed pantropic infection accompanied by hepatic necrosis, granuloprival cerebellar hypoplasia and hemorrhagic encephalopathy. Virological and serological studies showed that virus could persist in inoculated rats for at least 35 days and for at least 28 days after seroconversion was first detected. Immunohistochemical results indicated that RV-Y infects tissues conducive to virus excretion including kidney and lung. RV-Y also was found in genital tissues of some rats. Athymic juvenile rats inoculated intraperitoneally with RV-Y had a poor humoral immune response and harbored infectious virus for at least 3 weeks, whereas infection in euthymic control rats was detected for 1 week. These studies indicate that RV-Y can persists in the presence of humoral immunity and suggest that transmission of infection could occur for a substantial period after seroconversion. They also suggest that immunodeficient rats have increased susceptibility to persistent infection.

The pathogenesis of sialodacryoadenitis was studied in gnotobiotic CD rats inoculated intranasally with the causal virus. Virus replication was detected sequentially in the nasopharynx, tracheobronchial tree, cervical lymph nodes, submaxillary and parotid salivary glands, exorbital gland, and Harderian gland. Acute rhinitis appeared within 2 days after inoculation, and salivary glands had lesions in 4 days. Early changes in salivary and exorbital glands were characterized by necrosis of ductal epithelium, which rapidly progressed to widespread acinar necrosis, marked inflammation, edema and total effacement of glandular architecture. Harderian glands also had massive necrosis of tubuloalveolar units. Repair in all glands was characterized by marked squamous metaplasia of tubuloalveolar units. Repair in all glands was characterized by marked squamous metaplasia of ducts. Neutralizing and complement-fixing antibodies were detected in 7 days, and there was a concomitant decrease in tissue-virus titers. There was no detectable evidence for hematogenous spread of virus or for retrograde infection by way of major salivary ducts.