An interesting paper on HERVs

Expression of Human Endogenous Retrovirus Type K Envelope Protein is a Novel Candidate Prognostic Marker for Human Breast Cancer

I recently happened to read an interesting short report published in August 2011 issue of Genes and Cancer. In this study, the authors evaluated the use of expression of envelope (env) protein of human endogenous retroviruses-K (HERV-K) as a prognostic marker of breast cancer. HERVs constitute about 8% of human genome. There are many distinct families of HERVs present in human genome. Most of these families are defective and could not encode complete viruses. However, HERV-K family shows a conservation of seemingly intact retroviral genes as it is one of the most recently integrated viruses.   In a previously conducted study, the authors observed the expression of HERV-K env mRNA and protein in breast cancer tissues obtained from US women. To further study the role of HERV-K env mRNA as a prognostic marker for breast cancer, the authors looked at expression of HERV-K env mRNA and protein in breast cancer tissues obtained from both Chinese and US women. The authors also analyzed the relationship between HERV-K env expression and disease severity in these women.

Methodology and Results:

One hundred and twenty tissues from Chinese women including 40 breast cancer tissues, 40 matched adjacent uninvolved breast tissues and 40 breast tissues from benign breast diseases but not cancer were used in this study. HERV-K env mRNA was detected in 70% of breast cancer samples and 20% of surrounding uninvolved tissues from breast cancer patients. No HERV-K env mRNA was detected in breast tissues from control patients. Similar to mRNA results, HERV-K env protein expression was also higher in cancer tissues in comparison to controls. The authors also found medium to strong expression of env protein in cancerous tissues and weak to no expression in adjacent non-cancerous tissues.

The authors then looked at relationship between expression level of HERV-K protein and clinical features of the patients. 82% of the patients with high expression of HERV-K in their tumor had a tumor size greater than 3 cm. HERV-K env expression also correlated with other clinical and pathological characteristics in these patients. Furthermore, the scientists conducted a Kaplan-Meier survival analysis and found that the patients with high expression of HERV-K env protein had a significantly shorter overall survival in comparison with patients with moderate to low HERV-K env protein expression.

Taken together, all these results indicate that HERV-K env protein expression is highly upregulated in human breast cancer tissues and not in adjacent non-cancerous tissues or normal breast tissues.

In all the paper is nicely written and all the experiments seems to be nicely conducted. However, this paper exclusively talks about env but what about pol and gag? Expression of pol is particularly important as pol encodes for reverse transcriptase, which is required for production of new virus progenies.

The study did not observe any association between HERV-K env expression and ER/PR status. These results were surprising as earlier studies have observed that expression of HERV-K mRNA and protein was higher in breast cancer cell lines treated with estradiol and progesterone than in cells without treatment

Preterm infants' T cell responses to inactivated Poliovirus vaccine

I am writing a new blog after a long long time. Well, what a better way to start than this article published in 2009 issue of JID. http://jid.oxfordjournals.org/content/201/2/214.long

Background: Preterm infants are more susceptible to infection as their immune system is immature. earlier studies have examined humoral immune responses to many viral and bacterial vaccines in preterm infants. These studies have found disparity in antibody production between preterm and term infants. However, not much is known about T cell response to these vaccines in preterm infants. Since, adequate antibody production depends upon T cell help to B cells, the disparities in antibody production may reflect disparity in T cell responses in these two groups.
In the present study, the authors recruited 33 preterm and 50 term infants and studies their T cell response to vaccines.

Results: Of the 33 preterm infants, final results were available for 27 infants and of the 50 term infants, final results were available for 35 infants. First, the authors looked at the frequency of circulating CD4+ T cells in these two groups at 2 months and 7 months of age. There was no change in the frequency at these two time periods. Next, the authors looked at memory Cd4+ cells (Cd4+CD45RO+) in these infants. They observed that 7 month old preterm infants had fewer memory cells than seven month old term infants.
Furthermore, the authors stimulated CD4+ cells from both set of infants with Staphylococcus entertoxin B, Sabin Oral polio vaccine, serotype 3 strain and uninfected vero cell lysate by culturing whole blood with these in the presence of costimulatory monoclonal antibodies to CD28 and CD49d. Then they looked for percentage of CD4+ cells positive for CD69 and IFN-g. In response to stimulation with SEB, preterm infants had lower frequency of CD4+CD69+IFN-g+ cells than did term infants at 2 and seven months of age. The authors then compared the frequency of CD69+ and IFN-g+ cells among CD4 and CD45RO cells in both group of infants before and after vaccination with OPV serotype 3. Both the groups of infants developed a significant increase in poliovirus specific Cd69+IFg+ cells relative to prevaccination responses.
When the authors compared the CD69+ IFN-g+ responses between preterm and term infants after vaccination, they observed that frequency of CD4+CD69+, CD4+CD69+IFN-g+, CD4+CD45RO+CD69+ and CD4+CD45RO+CD69+IFN-g+ cells was comparable in two groups. To evaluate cell mediated immunity, PBMCs were isolated from both groups of infants (pre and post vaccination) and stimulated with OPV serotype 3. A positive proliferative response was defined as stimulation index of 3. It was observed that mean poliovirus-type 3 specific proliferation after vaccination was significantly lower in preterm infants than in term infants.
The authors next looked at neutralizing antibody response to all three subtypes of poliovirus in the sera of these infants after vaccination. All the infants showed neutralizing anitbodies post vaccination. There was no significant difference in geometric mean titer (GMT) to serotype 2 and 3 in the two groups of infants. However, GMT to serotype 1 was significantly low in preterm infants. To compare the safety of this vaccine in preterm and term infants, the authors looked for medically attended events (MAE) in both groups for 30 days. There were no significant events.

Discussion: The present study establishes that preterm infants, similar to term infants, generate a poliovirus type 3–specific T cell response and that the frequency of circulating poliovirus-specific responder T cells is comparable between preterm and term infants.
The study however, detected differences in circulating T cell populations between term and preterm infants.