Infected Offspring Research Articles

Infection without antibody response in mother‐to‐child transmission of HTLV‐I in rabbits

The presence or absence of the anti-human T-cell leukemia virus type (HTLV-I) antibody and the HTLV-I proviral genome was examined in the offspring of inbred rabbits, which were born to HTLV-I carrier does. The results showed that not all offspring born to the carriers were infected and that not all the infected offspring seroconverted at the age of 10 weeks, which is similar to observations made in human carriers. The anti-HTLV-I antibody was assayed by indirect immunofluorescence in 55 offspring at the age of 10 weeks, which were born to B/J or (B/J x Chbb:HM)F1 seropositive HTLV-I carrier does. Twelve out of 31 offspring born from F1 x F1 mating were seropositive, whereas none of 24 offspring born from B/J x B/J mating, F1 x B/J mating, or F1 x Chbb:HM mating were seropositive. The polymerase chain reaction (PCR) method revealed the presence of the HTLV-I proviral genome in 18 out of 23 offspring born from F1 x F1 mating (F2 hybrids). In these 18 HTLV-I-infected F2 hybrids, 8 were seropositive and 10 were seronegative. The major histocompatibility complex (MHC) of these 23 F2 hybrids was analyzed by restriction fragment length polymorphism (RFLP) in southern hybridization. The results showed no close correlation of MHC with HTLV-I susceptibility or with seroconversion. Natural infection via mother-to-child transmission of virus seems to produce seronegative as well as seropositive carriers. This rabbit model may be useful for the study of seronegative virus carriers via mother-to-child transmission of HTLV-I.

Outbreaks of border disease in goats induced by a pestivirus-contaminated orf vaccine, with virus transmission to sheep and cattle

Five herds with a total of 276 female goats experienced severe outbreaks of reproductive failure due to a pestivirus-contaminated experimental orf vaccine given early in the breeding season. The reproductive failures comprised barrenness in 42 goats, abortion in 53 and, in 118, the birth of dead or weak kids. The incidence of female goats with such failures was 82 per cent overall, herd incidence rates ranging from 79 to 96 per cent. No progeny showed characteristic signs of border disease (BD). Microscopic lesions in the CNS were moderate, mostly characterized by hypercellularity, cell disorganization and decreased myelin content. Non-cytopathic strains of pestivirus were demonstrated in tissue or serum from two weak-born and two apparently healthy kids. Neutralizing antibodies against a bovine pestivirus were found in all 254 goats examined about 4 months after vaccination. At the end of the breeding season, all kids were removed and 74 young kids were introduced from presumably normal herds. Approximately 8 months later, 64 (86 per cent) of the bought-in kids had pestivirus antibodies. Two years after the outbreaks, such antibodies were found in all but three of 127 vaccinated goats still alive, and another 2 years later, in all 22 vaccinated goats in one of the herds. Sheep also were kept on the same five farms and cattle on one. Sheep in two of the flocks showed reproductive failure probably caused by pestivirus transmitted from infected goat offspring. A pair of twin lambs showed nervous signs and brain lesions characteristic of BD, while 17 other lambs had a very low growth rate. Virus was not isolated from any lamb. The prevalence rates of ewes with pestivirus antibodies in the two affected flocks were 33 and 72 per cent, respectively. One of nine cows aborted a pestivirus-infected foetus, and all were antibody-positive.

Studies on the Biology of Phleboviruses in Sand Flies (Diptera: Psychodidae)

This paper describes a series of experiments which were done to determine the behavior of 14 different phleboviruses in laboratory-reared sand flies (Phlebotomus papatasi, P. perniciosus and Lutzomyia longipalpis) after oral and parenteral infection. Most of the viruses replicated in the sand flies after intrathoracic inoculation; however, the insects were quite refractory to oral infection. Six of 11 phleboviruses tested were transovarially transmitted in one or more sand fly species. The percentage of infected F1 offspring produced by parenterally infected female parents ranged from 1.5-60%, depending on the virus type used. These data support the hypothesis that some of the phleboviruses are maintained in sand flies by transovarial transmission.

Cytomegalovirus: genetic variation of viral genomes.

Genomic complexity of human CMV is one of the largest among various DNA viruses. With such genome complexity and widespread distribution, even a minimal frequency of mutation will be enough to create a complicated genetic heterogeneity in this virus. The virus genome is relatively stable during subcultivation in tissue culture. Variants with minor modification in restriction enzyme sites do gradually develop. These variants share substantial restriction fragment pattern homology with the parental virus. Virus DNA has a molecular weight of 150 X 10(6) daltons for a complete genome. The DNA contains 2 covalently linked L and S components which are separated by internal inverted repetitious sequences of both terminal-end sequences. L and S components are oriented invertably with 4 isomeric arrangements. No tandem repeated sequences have been found. Based on DNA restriction pattern analysis, we conclude that the majority of recurrent infections represent reactivation of existing latent viruses; however, reinfections by a new virus strain do occur occasionally. By studying virus strains isolated from the consecutive congenitally infected infants and strains from mothers and their congenitally infected offspring, we furthermore conclude that the latent virus in women is relatively stable genetically. Moreover, the virus strains after being transmitted to the offspring are still genetically similar to that of the mothers. As in vitro, spontaneous minor variations occur after the in vivo residence. In a long period of evolution the accumulation of minor variations might create great diversity with major similarity.

Transovarial Transmission of Yellow Fever Virus by Mosquitoes (Aedes Aegypti)

Female Aedes aegypti mosquitoes infected with yellow fever virus by intrathoracic inoculation transmitted the virus to a small percentage of their F1 progeny. Infected offspring were obtained from surface-sterilized as well as from untreated eggs, indicating that the virus was transovarially transmitted. Vertical transmission of yellow fever virus in mosquitoes may be an alternative mechanism for biological survival of the virus during adverse periods or in the absence of susceptible vertebrate hosts.

Latent herpes cervicitis and mixed cervical carcinoma

diovascular defects or cataracts or simply the presence of a lymphocyte transforming agent in the cord blood of an otherwise asymptomatic neonate. • 4 This report documents severe, multiple congenital anomalies in an infant exposed to the EBV from conception to delivery. It differs from previously reported cases in its widespread tissue involvement, possibly representing the congenital infection in its severest form. The EBV may cause a spectrum of involvement in the congenitally infected offspring ranging from the subclinical type to severe deformity and death. Its incidence is difficult to define, but it is probably an uncommon cause of congenital malformation. The absence of cord blood IgM levels in our patient is consistent with the report of Chang and Blankenshipa in that infection occurred prior to the development of immunocompetency in the fetus. Also, congenitally infected infants with low cord blood lgM levels were stillborn or died in utero with significantly greater frequency. The place of the EB V in perinatal infections is strongly implied both by its close physical relationship to other known viral teratogens and by the spectrum of perinatal involvement just described. The question of its importance and prevalence as a teratogen cannot be answered at this time.

808 CELL MEDIATED IMMUNITY IN MOTHERS AND THEIR OFFSPRING WITH CYTOMEGALOVIRUS (CMV) INFECTION

Lymphocyte transformation to CMV was determined for 7 patients with natal (N-CMV) and 17 with congenital (C-CMV) infection as well as their mothers. Antigens consisted of heat inactivated intracellular virus and a control. All subjects were tested against strain AD169 and ½ of them against a clinical isolate. The mean stimulation index (S.I.) of 11 seronegative adults was 0.7 (± 0.3) irrespective of the sera used. Mean indices for 10 seropositive normal adults were 21.7 in autologous sera (A.S.) and 34.8 in homologous seropositive sera (H.S.). Of the 7 children with N-CMV, 1/7 responded in A.S. and 2/2 in H.S. (mean maximal S.I. {m.m.S.I.}, 3.3). Among the 15 with inapparent C-CMV, 4/14 were positive in A.S. and 7/9 in H.S. for a total of 9 responders (m.m.S.I., 7.5). Neither of 2 with disease were positive. For the total group, 3/13 at ≥12 months of age reacted whereas 7/11 over 12 months did so. Seven of 9 mothers of children with N-CMV were positive as follows: 5/7 in A.S. and 3/3 in H.S. (m.m.S.I., 11.4). Among women with congenitally infected offspring, 13 of 15 responded, i.e., 7/14 in A.S. and 6/9 in H.S. (m.m.S.I., 8.4). Both mothers of affected infants reacted (m.m.S.I., 3.6). Among the 23 responding patients assayed in both sera, 9 stimulated in H.S. only whereas the converse was observed only once in this group and not at all in normal adult controls. In general, both antigens stimulated equally well; however, 3 children and 1 mother failed to respond to the wild strain.

Vertical transmission of La Crosse virus (California encephalitis group): transovarial and filial infection rates in Aedes triseriatus (Diptera: Culicidae).

La Crosse (LAC) virus remained infective to warm-blooded hosts after 8 successive transovarial passages in the mosquito Aedes triseriatus . Virtually all transovarially infected females (98%) transmitted LAC virus to their offspring, and the mean percentage of infected offspring from an infected female was 71%, a rate that remained essentially constant from one generation to the next. These results indicate that the virus can persist 4 years or longer in the absence of horizontal amplification in vertebrate hosts and the data provide a basis for estimating, during anyone season, the amount of amplification necessary to maintain the virus at existing endemic levels.

Prevention of murine sarcoma virus oncogenesis in offspring of immunized female mice.

BALB/c mice born to and nursed by females immunized against MSV-M showed a reduced tumour incidence and a high tumour regression rate following MSV-M injection at 7-14 days of age. Females immunized long before mating could also confer protection to their offspring whereas females immunized after parturition could not. A reduced number of tumours was observed in 3 out of 14 MSV-M injected litters whose mothers had been previously exposed to the virus while nursing infected offspring. Sera from suckling mice born to and nursed by immunized mothers contained MSV-M neutralizing antibody as shown by an in vitro focus reduction assay. Cell-free extracts from mice which developed leukaemia after MSV-M inoculation were tested for oncogenic activity in 1-week old mice. Out of 6 extracts, 4 induced typical MSV-M tumours and 2 caused leukaemias.