Viral structure of Herpes simplex virus

Animal herpes viruses all share some common properties. The structure of herpes viruses consists of a relatively large double-stranded, linear DNA genome encased within an icosahedral protein cage called the capsid, which is wrapped in a lipid bilayer called the envelope. The envelope is joined to the capsid by means of a tegument. This complete particle is known as the virion. HSV-1 and HSV-2 each contain at least 74 genes (or open reading frames, ORFs) within their genomes,[13] although speculation over gene crowding allows as many as 84 unique protein coding genes by 94 putative ORFs. These genes encode a variety of proteins involved in forming the capsid, tegument and envelope of the virus, as well as controlling the replication and infectivity of the virus. These genes and their functions are summarized in the table below.

The genomes of HSV-1 and HSV-2 are complex and contain two unique regions called the long unique region (UL) and the short unique region (US). Of the 74 known ORFs, UL contains 56 viral genes, whereas US contains only 12. Transcription of HSV genes is catalyzed by RNA polymerase II of the infected host. Immediate early genes, which encode proteins that regulate the expression of early and late viral genes, are the first to be expressed following infection. Early gene expression follows, to allow the synthesis of enzymes involved in DNA replication and the production of certain envelope glycoproteins. Expression of late genes occurs last; this group of genes predominantly encode proteins that form the virion particle.

Five proteins from (UL) form the viral capsid; UL6, UL18, UL35, UL38 and the major capsid protein UL19.

Cellular entry:
Entry of HSV into the host cell involves interactions of several glycoproteins on the surface of the enveloped virus, with receptors on the surface of the host cell. The envelope covering the virus particle, when bound to specific receptors on the cell surface, will fuse with the host cell membrane and create an opening, or pore, through which the virus enters the host cell.

The sequential stages of HSV entry are analogous to those of other viruses. At first, complementary receptors on the virus and the cell surface bring the viral and cell membranes into proximity. In an intermediate state, the two membranes begin to merge, forming a hemifusion state. Finally, a stable entry pore is formed through which the viral envelope contents are introduced to the host cell. The virus can also be endocytosed after binding to the receptors, and the fusion could occur at the endosome.


In the case of a herpes virus, initial interactions occur when two viral envelope glycoprotein called glycoprotein C (gC) and glycoprotein B (gB) bind to a cell surface particle called heparan sulfate. Next, the major receptor binding protein, glycoprotein D (gD), binds specifically to at least one of three known entry receptors. These include herpesvirus entry mediator (HVEM), nectin-1 and 3-O sulfated heparan sulfate. The receptor provides a strong, fixed attachment to the host cell. These interactions bring the membrane surfaces into mutual proximity and allow for other glycoproteins embedded in the viral envelope to interact with other cell surface molecules. Once bound to the HVEM, gD changes its conformation and interacts with viral glycoproteins H (gH) and L (gL), which form a complex. The interaction of these membrane proteins results in the hemifusion state. Afterward, gB interaction with the gH/gL complex creates an entry pore for the viral capsid.[15] gB interacts with glycosaminoglycans on the surface of the host cell.

Know about Herpes simplex

also known as human herpesvirus 1 and 2 (HHV-1 and HHV-2), are two members of the herpesvirus family, Herpesviridae, that infect humans.[1] Both HSV-1 (which produces most cold sores) and HSV-2 (which produces most genital herpes) are ubiquitous and contagious. They can be spread when an infected person is producing and shedding the virus. Herpes simplex can be spread through contact with saliva, such as sharing drinks.

Symptoms of herpes simplex virus infection include watery blisters in the skin or mucous membranes of the mouth, lips or genitals. Lesions heal with a scab characteristic of herpetic disease. Sometimes, the viruses cause very mild or atypical symptoms during outbreaks. However, as neurotropic and neuroinvasive viruses, HSV-1 and -2 persist in the body by becoming latent and hiding from the immune system in the cell bodies of neurons. After the initial or primary infection, some infected people experience sporadic episodes of viral reactivation or outbreaks. In an outbreak, the virus in a nerve cell becomes active and is transported via the neuron's axon to the skin, where virus replication and shedding occur and cause new sores. It is one of the most common sexually transmitted infections.

HSV-1 and -2 are transmitted by contact with an infected area of the skin during reactivations of the virus. Herpes simplex virus (HSV)-2 is periodically shed in the human genital tract, most often asymptomatically, and most sexual transmissions occur during asymptomatic shedding. Asymptomatic reactivation means that the virus causes atypical, subtle or hard to notice symptoms that are not identified as an active herpes infection. In one study, daily genital swab samples found HSV-2 at a median of 12-28% of days among those who have had an outbreak, and 10% of days among those suffering from asymptomatic infection, with many of these episodes occurring without visible outbreak ("subclinical shedding").

In another study, seventy-three subjects were randomized to receive valaciclovir 1 g daily or placebo for 60 days each in a 2-way crossover design. A daily swab of the genital area was self-collected for HSV-2 detection by polymerase chain reaction, in order to compare the effect of valaciclovir 1 g once daily for 60 days versus placebo on asymptomatic viral shedding in immunocompetent, HSV-2 seropositive subjects without a history of symptomatic genital herpes infection. The study found that valaciclovir significantly reduced shedding during subclinical days compared to placebo, showing a 71% reduction. 84% of subjects had no shedding while receiving valaciclovir versus 54% of subjects on placebo. 88% of patients treated with valaciclovir had no recognized signs or symptoms versus 77% for placebo.

For HSV-2, subclinical shedding may account for most of the transmission, and one study found that infection occurred after a median of 40 sex acts. Atypical symptoms are often attributed to other causes such as a yeast infection. HSV-1 is often acquired orally during childhood. It may also be sexually transmitted, including contact with saliva, such as kissing and mouth-to-genital contact (oral sex). HSV-2 is primarily a sexually transmitted infection, but rates of HSV-1 genital infections are increasing.

Both viruses may also be transmitted vertically during childbirth, although the real risk is very low.[10] The risk of infection is minimal if the mother has no symptoms or exposed blisters during delivery. The risk is considerable when the mother is infected with the virus for the first time during late pregnancy.

Aciclovir Adverse effects

Common adverse drug reactions (≥1% of patients) associated with systemic aciclovir therapy (oral or IV) include: nausea, vomiting, diarrhea, encephalopathy (with IV use only), injection site reactions (with IV use only) and headache. In high doses, hallucinations have been reported. Infrequent adverse effects (0.1–1% of patients) include: agitation, vertigo, confusion, dizziness, oedema, arthralgia, sore throat, constipation, abdominal pain, hair loss, rash and weakness. Rare adverse effects (<0.1% of patients) include: coma, seizures, neutropenia, leukopenia, crystalluria, anorexia, fatigue, hepatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis, thrombotic thrombocytopenic purpura and anaphylaxis.

Intravenous aciclovir may cause reversible nephrotoxicity in up to 5% to 10% of patients because of precipitation of aciclovir crystals in the kidney. Aciclovir crystalline nephropathy is more common when aciclovir is given as a rapid infusion and in patients with dehydration and preexisting renal impairment. Adequate hydration, a slower rate of infusion, and dosing based on renal function may reduce this risk.

What is Leukopenia

also known as leukocytopenia or leucopenia, from Greek λευκός "white" and πενία "deficiency") is a decrease in the number of white blood cells (leukocytes) found in the blood, which places individuals at increased risk of infection.

Neutropenia, a subtype of leukopenia, refers to a decrease in the number of circulating neutrophil granulocytes, the most abundant white blood cells. The terms leukopenia and neutropenia may occasionally be used interchangeably, as the neutrophil count is the most important indicator of infection risk. This should not be confused with agranulocytosis.

Some medications can have an impact on the number and function of white blood cells.

Medications which can cause leukopenia include clozapine, an antipsychotic medication with a rare adverse effect leading to the total absence of all granulocytes (neutrophils, basophils, eosinophils). The antidepressant and smoking addiction treatment drug bupropion HCl (Wellbutrin) can also cause leukopenia with long-term use. Minocycline, a commonly prescribed antibiotic, is another drug known to cause leukopenia. There are also reports of leukopenia caused by divalproex sodium or valproic acid (Depakote), a drug used for epilepsy (seizures), mania (with bipolar disorder) and migraine.

The anticonvulsant drug, lamotrigine, has been associated with a decrease in white blood cell count.

The FDA monograph for metronidazole states that this medication can also cause leukopenia, and the prescriber information suggests a complete blood count, including differential cell count, before and after, in particular, high dose therapy.

Other medications include immunosuppressive drugs, such as sirolimus, mycophenolate mofetil, tacrolimus, cyclosporine, Leflunomide (Arava) and TNF inhibitors. Interferons used to treat multiple sclerosis, such as Rebif, Avonex, and Betaseron, can also cause leukopenia.

Chemotherapy targets cells that grow rapidly, such as tumors, but can also affect white blood cells, because they are characterized by bone marrow as rapid growing. A common side effect of cancer treatment is neutropenia, the lowering of neutrophils (a specific type of white blood cell).


Decreased white blood cell count may be present in cases of arsenic toxicity.

Drug Condition:
Low white cell count may be due to acute viral infections, such as with a cold or influenza. It can be associated with chemotherapy, radiation therapy, myelofibrosis and aplastic anemia (failure of white cell, red cell and platelet production). HIV and AIDS are also a threat to white cells.

Other causes of low white blood cell count include systemic lupus erythematosus, Hodgkin's lymphoma, some types of cancer, typhoid, malaria, tuberculosis, dengue, rickettsial infections, enlargement of the spleen, folate deficiencies, psittacosis, sepsis and Lyme disease. Many other causes exist, such as deficiency in certain minerals, such as copper and zinc.


Pseudoleukopenia can develop upon the onset of infection. The leukocytes (predominately neutrophils, responding to injury first) start migrating towards the site of infection and can be scanned at the site of infection. Their migration causes bone marrow to produce more WBCs to combat infection as well as to restore the leukocytes in circulation, but as the blood sample is taken upon the onset of infection, it contains low amount of WBCs, which is why it is called "pseudoleukopenia".

What is Zidovudine

Zidovudine, also known as azidothymidine (AZT), is an antiretroviral medication used to prevent and treat HIV/AIDS.

It is of the nucleoside analog reverse-transcriptase inhibitor (NRTI) class. AZT inhibits the enzyme (reverse transcriptase) that HIV uses to synthesize DNA, thus preventing viral DNA from forming.

AZT was the first U.S. government-approved treatment for HIV, marketed under the brand name Retrovir. AZT was the first breakthrough in AIDS therapy, significantly reducing the replication of the virus and leading to clinical and immunologic improvements. It can also be used to prevent HIV transmission, such as from mother to child during the period of birth or after a needle stick injury. Used by itself in HIV-infected patients, AZT slows HIV replication in patients, but does not stop it entirely.[4] HIV may become AZT-resistant over time, and therefore AZT is now usually used in conjunction with other anti-HIV drugs in the combination therapy called highly active antiretroviral therapy (HAART). AZT is included in Combivir and Trizivir, and is included in the World Health Organization's Model List of Essential Medicines, which suggests the minimum medicinal needs for a basic health care system.

HIV treatment:
Treatment regimens involve relatively low dosages of AZT taken just twice a day, almost always as part of highly active antiretroviral therapy (HAART), in which AZT is combined with other drugs (known informally as "the triple cocktail") in order to prevent the selection of HIV into an AZT-resistant form.


AZT has been used as post-exposure prophylaxis (PEP) in combination with another antiretroviral, lamivudine, substantially reducing the risk of HIV infection following the first single exposure to the virus (such as a needle-stick injury involving blood or body fluids from an individual known or suspected of being infected with HIV) (though its use in PEP has largely been replaced by tenofovir as a component of a three drug combination).

AZT is now a principal part of the clinical pathway for both pre-exposure prophylaxis and post-exposure treatment of mother-to-child transmission of HIV during pregnancy, labor, and delivery and has been proven to be integral to uninfected siblings' perinatal and neonatal development. Without AZT, as many as 10 to 15% of fetuses with HIV-infected mothers will themselves become infected. AZT has been shown to reduce this risk to as little as 8% when given in a three-part regimen post-conception, delivery, and six weeks post-delivery. Consistent and proactive precautionary measures, such as the rigorous use of antiretroviral medications, cesarean section, face masks, heavy-duty rubber gloves, clinically segregated disposable diapers, and avoidance of mouth contact will further reduce child-attendant transmission of HIV to as little as 1–2%.

During the period from 1994 to 1999 when this was the primary form of prevention of mother-to-child HIV transmission, AZT prophylaxis prevented more than 1000 parental and infant deaths from AIDS in the United States. In the US at this time, the accepted standard of care for HIV-positive mothers was known as the 076 regimen and involved 5 daily doses of AZT from the second trimester onwards as well as AZT intravenously administered during labour. As this treatment was lengthy and expensive, it was deemed unfeasible in the global south, where mother-to-child transmission was a significant problem. A number of studies were initiated in the late 1990s that sought to test the efficacy of a shorter, simpler regimen for use in ‘resource-poor’ countries. This AZT short course was an inferior standard of care and would have been considered malpractice if trialed in the US; however it was nonetheless a treatment that would improve (at least to some extent) the care and survival of impoverished subjects, given local realities and the “shortages of staffing, medication and equipment that bound the possibilities of care” in such settings. The trials were highly controversial and highlighted the inability of researchers to align the local realities, such as the inaccessibility of the AZT, with the scientific and ethical protocols designed in ‘resource-rich’ countries.

Know about acyclovir

Common adverse drug reactions (≥1% of patients) associated with systemic aciclovir therapy (oral or IV) include: nausea, vomiting, diarrhea, encephalopathy (with IV use only), injection site reactions (with IV use only) and headache. In high doses, hallucinations have been reported. Infrequent adverse effects (0.1–1% of patients) include: agitation, vertigo, confusion, dizziness, oedema, arthralgia, sore throat, constipation, abdominal pain, hair loss, rash and weakness. Rare adverse effects (<0.1% of patients) include: coma, seizures, neutropenia, leukopenia, crystalluria, anorexia, fatigue, hepatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis, thrombotic thrombocytopenic purpura and anaphylaxis.

Aciclovir , also known as acyclovir and acycloguanosine, is an antiviral medication. It is primarily used for the treatment of herpes simplex virus infections, chickenpox, and shingles. Other uses include prevention of cytomegalovirus infections following transplant and infections due to Epstein-Barr virus. It is available by mouth and intravenously.

Common side effects include nausea and diarrhea. Potentially serious side effects include kidney problems and low platelets. Greater care is recommended in those with poor liver or kidney function. It is generally considered safe for use in pregnancy with no harms having been observed. It is safe during breastfeeding. Aciclovir is a nucleic acid analogue made from guanosine. It works by decreasing the making of the virus's DNA.

The discovery of aciclovir was announced in 1977. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system. It is available as a generic medication and is marketed under many brand names worldwide. The wholesale cost is between 0.03 and 0.12 USD per dose. In the United States it is not very expensive at about 0.50 USD per dose.

Know about Acne

Acne vulgaris is a chronic skin disease of the pilosebaceous unit and develops due to blockages in the skin's hair follicles. These blockages are thought to occur as a result of the following four abnormal processes: a higher than normal amount of sebum production (influenced by androgens), excessive deposition of the protein keratin leading to comedone formation, colonization of the follicle by Propionibacterium acnes (P. acnes ) bacteria, and the local release of pro-inflammatory chemicals in the skin. Severe acne is inflammatory, but acne can also be noninflammatory.

Acne vulgaris  is a long-term skin disease that occurs when hair follicles become clogged with dead skin cells and oil from the skin. Acne is characterized by areas of blackheads, whiteheads, pimples, and greasy skin, and may result in scarring. The resulting appearance can lead to anxiety, reduced self-esteem and, in extreme cases, depression or thoughts of suicide.

Genetics is thought to be the cause in 80% of cases. The role of diet and cigarette smoking is unclear while neither cleanliness nor sunlight appear to be involved. Acne primarily affects skin with a greater number of oil glands, including the face, upper part of the chest, and back. During puberty, in both sexes, acne is often brought on by an increase in androgens such as testosterone. Excessive growth of the bacteria Propionibacterium acnes, which is normally present on the skin, is often involved.

Many treatment options are available to improve the appearance of acne, including lifestyle changes, procedures, and medications. Eating fewer simple carbohydrates like sugar may help. Topical azelaic acid, benzoyl peroxide, and salicylic acid are commonly-used treatments. Antibiotics and retinoids are available in both topical and oral formulations to treat acne. However, resistance to antibiotics may develop. A number of birth control pills may be useful for preventing acne in women. Oral isotretinoin is usually reserved for severe acne due to greater potential side effects. Early and aggressive treatment is advocated by some to lessen the overall long-term impact to individuals.

Acne occurs most commonly during adolescence, affecting an estimated 80–90% of teenagers in the Western world. Lower rates are reported in some rural societies. In 2010, acne was estimated to affect 650 million people globally, making it the 8th most common disease worldwide. People may also be affected before and after puberty. Though it becomes less common in adulthood than in adolescence, nearly half of people in their twenties and thirties continue to have acne. About 4% continue to have difficulties into their forties.